LUANAN

B GIO DC V O TO
VIN HN LM KHOA HC V
CNG NGH VIT NAM
VIN HO HC
TRNG TH THU HIN
NGHIN CU THNH PHN HA HC V HOT TNH

SINH HC CY DU DU L NHN
(Tetradium glabrifolium (Benth.) Hartl.)
LUN N TIN S HA HC
H NI, 2014
B GIO DC V O TO
VIN HN LM KHOA HC V
CNG NGH VIT NAM
VIN HO HC
TRNG TH THU HIN
NGHIN CU THNH PHN HA HC V HOT TNH

SINH HC CY DU DU L NHN
Tetradium glabrifolium (Benth.) Hartl.
LUN N TIN S HA HC
Chuyn ngnh:
Ho hc hu c
M s:
62.44.27.01
Hng dn khoa hc: 1. PGS. TS. Phan Vn Kim

2. GS. TS. Nguyn Vn Tuyn
H NI, 2014
LI CAM OAN
Ti xin cam oan lun n ny l cng trnh nghin cu ca ring ti di s
hng dn khoa hc ca PGS.TS. Phan Vn Kim v GS.TS. Nguyn Vn Tuyn.
Cc s liu, kt qu trong lun n l trung thc v cha c cng b trong bt k
cng trnh no khc.
Tc gi
Trng Th Thu Hin
LI CM N
Lun n ny c hon thnh ti Vin Ha sinh bin v Vin Ho hc - Vin
Hn lm Khoa hc v Cng ngh Vit Nam. Trong qu trnh nghin cu, tc gi
nhn c nhiu s gip qu bu ca cc thy c, cc nh khoa hc, cc ng
nghip, bn b v gia nh.
Ti xin by t li cm n su sc, s cm phc v knh trng nht ti PGS.
TS. Phan Vn Kim v GS. TS. Nguyn Vn Tuyn - nhng ngi Thy tn tm
hng dn khoa hc, ng vin, khch l v to mi iu kin thun li nht cho ti
trong sut thi gian thc hin lun n.
Ti xin trn trng cm n Ban lnh o Vin Ha sinh bin v Ban lnh o
Vin Ha hc cng tp th cn b ca hai Vin quan tm gip v to mi
iu kin thun li cho ti trong sut qu trnh hc tp v nghin cu.
Ti xin chn thnh cm n phng Nghin cu cu trc - Vin Ha Sinh bin,
c bit l TS. Hong L Tun Anh, TS. Nguyn Xun Nhim, TS. Phm Hi Yn,
TS. Nguyn Vn Thanh v CN. an Th Thy Hng v s ng h to ln, nhng li
khuyn b ch v nhng gp qu bu trong vic thc hin v hon thin lun n.
Ti xin trn trng cm n Phng Hp cht t nhin, i hc Osaka, Nht
Bn gip ti trong vic sng lc v th hot tnh khng lao.
Ti xin chn thnh cm n ti cc ng nghip ti B mn c hc v
phng x qun s - Hc vin Qun Y v Ban Gim c Hc vin Qun y ng h
v to iu kin thun li cho ti trong sut thi gian lm nghin cu sinh.
Ti xin by t lng bit n chn thnh v su sc nht ti ton th gia nh,
bn b v nhng ngi thn lun lun quan tm, khch l, ng vin ti trong
sut qu trnh hc tp v nghin cu.
Xin trn trng cm n!
Tc gi
Trng Th Thu Hin

ii
MC LC
DANH MC CH VIT TT................................................................................. vi

DANH MC BNG ............................................................................................... viii
DANH MC HNH ....................................................................................................x
M U .....................................................................................................................1
CHNG 1 TNG QUAN TI LIU ......................................................................3
1.1. GII THIU V CHI TETRADIUM ...............................................................3
1.1.1. c im thc vt chi Tetradium ..............................................................3
1.1.2 Cc nghin cu v thnh phn ha hc ca chi Tetradium .......................4
1.1.2.1. Cc hp cht alkaloid ...........................................................................7
1.1.2.2. Cc hp cht triterpenoid ...................................................................10
1.1.2.3. Cc hp cht limonoid .......................................................................11
1.1.2.4. Cc hp cht flavonoid ......................................................................13
1.1.2.5. Cc hp cht coumarin ......................................................................14
1.1.2.6. Cc hp cht benzenoid .....................................................................15
1.1.2.7. Cc hp cht sterol .............................................................................16
1.1.2.8. Cc hp cht khc ..............................................................................16
Kt lun ...........................................................................................................17
1.1.3. Cc nghin cu v hot tnh sinh hc ca chi Tetradium .......................18
1.1.3.1. Tc dng khng ung th.....................................................................18
1.1.3.2. Tc dng vi h tim mch..................................................................19
1.1.3.3. Tc dng i vi h thn kinh ...........................................................21
1.1.3.4. Tc dng khng vim, gim au ........................................................21
1.1.3.5. Cc tc dng khc ..............................................................................22
Kt lun ...........................................................................................................26
1.2. Gii thiu v cy du du l nhn ..................................................................27
1.2.1. c im thc vt ...................................................................................27
1.2.2. Cng dng cha bnh..............................................................................27
1.2.3. Tnh hnh nghin cu trn th gii ..........................................................28
1.2.4. Tnh hnh nghin cu Vit Nam ..........................................................29
Kt lun .............................................................................................................29
CHNG 2 I TNG V PHNG PHP NGHIN CU .........................30
2.1. Mu thc vt ..................................................................................................30
2.2. Phng php phn lp cc hp cht...............................................................30
iii
2.3. Phng php xc nh cu trc ha hoc ........................................................31

2.4. Phng php xc nh hot tnh sinh hc .....................................................32
CHNG 3 THC NGHIM V KT QU ........................................................39
3.1. Phn lp cc hp cht t cy du du l nhn................................................39
3.1.1. Phn lp cc hp cht t mu l ca cy du du l nhn ......................39
3.1.2. Phn lp cc hp cht t mu v thn ca cy du du l nhn .............41
3.2. Hng s vt l v d kin ph ca cc hp cht phn lp c t cy du du
l nhn ...................................................................................................................44
CHNG 4 KT QU V THO LUN .............................................................50
4.1. Phn lp cc hp cht t cy du du l nhn................................................50
4.2 Xc nh cu trc cc hp cht .......................................................................51
4.2.1. Hp cht TG1 (cht mi): Tetraglabrifolioside......................................51
4.2.2. Hp cht TG2: 6-Acetonyl-N-methyldihydrodecarine ..........................58
4.2.3. Hp cht TG3: 6-Acetonyldihydrochelerythrine ...................................64
4.2.4. Hp cht TG4: Decarine .........................................................................66
4.2.5. Hp cht TG5: Iwamide .........................................................................68
4.2.6. Hp cht TG6: Rutaecarpine ..................................................................72
4.2.7. Hp cht TG7: 12-Hydroxyevodol ......................................................74
4.2.8. Hp cht TG8: Rutaevine .......................................................................79
4.2.9. Hp cht TG9: Lupeol ............................................................................83
4.2.10. Hp cht TG10: Friedelan-3-one..........................................................85
4.2.11. Hp cht TG11: Phellamurin................................................................90
4.2.12. Hp cht TG12: Epimedoside C...........................................................95
4.2.13. Hp cht TG13: Astragalin ..................................................................97
4.2.14. Hp cht TG14: Nicotiflorin ................................................................98
4.2.15. Hp cht TG15: Trifoline ...................................................................104
4.2.16. Hp cht TG16: Quercetin .................................................................105
4.2.17. Hp cht TG17: -Tocopherol ...........................................................106
4.2.18. Hp cht TG18: (2E,4E) N-Isobutyltetradeca-2,4-dienamide............110
4.2.19. Hp cht TG19: (2E,4E)-N-Isobutyldeca-2,4-dienamide ..................115
4.2.20. Hp cht TG20: (2E,4E,8E)-N-Isobutyltetradeca-2,4,8-trienamide ..117
4.2.21. Hp cht TG21: Syringin ...................................................................119
4.2.22. Hp cht TG22: Saikolignannisode A................................................120
4.2.23. Hp cht TG23: Picraquassioside D ..................................................122
iv
4.2.24. Hp cht TG24: Stigmatsterol ............................................................123

4.2.25. Hp cht TG25: Daucosterol ..............................................................125
4.2.26. Hp cht TG26: 5-Hydroxymethylfurfural ........................................127
Kt lun: ..........................................................................................................128
4.3. Kt qu th hot tnh sinh hc .....................................................................131
4.3.1. Kt qu kim tra hot tnh gy c t bo in vitro ................................131
4.3.2. Kt qu kim tra hot tnh khng lao ....................................................132
4.3.3. Kt qu kim tra hot tnh chng oxi ha .............................................133
4.3.4. Kt qu kim tra hot tnh khng vi sinh vt kim nh .......................134
Kt lun: ..........................................................................................................135
KT LUN .............................................................................................................137
KIN NGH ............................................................................................................138
CC CNG TRNH CNG B LIN QUAN N LUN N ..................139
TI LIU THAM KHO.......................................................................................140
PH LC .................................................................................................................... I
Ph lc 1. Ph khi lng phn gii cao v ph NMR ca TG3. ............................ II
Ph lc 2. Ph NMR ca TG4. .................................................................................. V
Ph lc 3. Ph khi lng phn gii cao v ph NMR ca TG6. ......................... VIII
Ph lc. Ph NMR ca TG9. .................................................................................. XII
Ph lc 5. Ph NMR ca TG12. ............................................................................. XV
Ph lc 6. Ph khi lng v ph NMR ca TG13............................................ XVIII
Ph lc 7. Ph khi lng v ph NMR ca TG15............................................. XXII
Ph lc 8. Ph NMR ca TG16. .........................................................................XXVI
Ph lc 9. Ph khi lng phn gii cao v ph NMR ca TG19. .................. XXVII
Ph lc 10. Ph khi lng phn gii cao v ph NMR ca TG20. ..................XXXI
Ph lc 11. Ph khi lng phn gii cao v ph NMR ca TG21. ............... XXXIV
Ph lc 12. Ph NMR ca TG22. .................................................................. XXXVII
Ph lc 13. Ph NMR ca TG23. .......................................................................... XLI
Ph lc 14. Ph khi lng v ph NMR ca TG24.......................................... XLIV
Ph lc 15. Ph khi lng phn gii cao v ph NMR ca TG25. .................. XLVI
Ph lc 16. Ph khi lng phn gii cao v ph NMR ca TG26. .................. XLIX
Ph lc 17. Kt qu xc nh hot tnh khng vi sinh vt kim nh..................... LII
DANH MC CH VIT TT
K hiu
13
C-NMR
c.c
CCR
CGRP
Ting Anh
Carbon-13 Nuclear Magnetic
Resonance Spectroscopy
Proton Nuclear Magnetic
Resonance Spectroscopy
5-hydroxytryptamine (hay
Serotonin)
Column chromatography
CC chemokine receptor
Calcitonin gene related peptide
COX
Cyclooxygenase
DEPT
Distortionless Enhancement by
Polarisation Transfer
Dimethyl sulfoxide
1,1- diphenyl -2-picrylhydrazyl
Effective concentration at 50%
H-NMR
5-HT
DMSO
DPPH
EC50
ESI-MS
Fl
Gal
GI50
Electron Spray Ionization Mass

Spectra
Fibril sarcoma of Uteus
Galactopyranoside
Grow inhibitory at 50%
Glc
HeLa
HepG2
HMBC
Glucopyranoside
Henrietta lacks
Human hepatocellular carcinoma
Heteronuclear mutiple Bond
Connectivity
HR-ESI-MS High Resolution Electronspray
Ionization Mass Spectrum
HPLC
High Performance Liquid
Chromatography
HSQC
Heteronuclear Single-Quantum
Coherence
IC50
Inhibitory concentration at 50%
ID50
iNOS
Inhibitory dose at 50%

Inducible nitric oxide synthase
KB
Human epidemoid carcinoma

vi
Din gii
Ph cng hng t ht nhn
cacbon 13
Ph cng hng t ht nhn
proton
5-hydroxytryptamine
Sc k ct
Th th CC chemokine
i khng th th peptid lin
h n gen calcitonin
Enzyme hnh thnh cc cht
trung gian sinh hc prostanoid
Ph DEPT
Nng gy ra tc ng sinh
hc cho 50% i tng th
nghim
Ph khi lng ion ha phun m
in t
Ung th mng t cung
Kh nng c ch tng trng 50
%
Ung th c t cung
Ung th gan ngi
Ph tng tc d ht nhn qua
nhiu lin kt
Ph khi lng phn gii cao
phun m in t
Sc k lng hiu nng cao
Ph tng tc d ht nhn qua 1
lin kt
Nng c ch 50% i tng
th nghim
Liu c ch ti thiu 50%
Mt enzyme to ra nitric oxide
t amino L-arginine acid
Ung th biu m ngi
KH
LNCaP
LU
MIC
NOS
OD
Rha
ROS
RD
RP18
PGE2
TCA
TGF-
TLC
TMS
TNF-
TPH
SC
SW480
Xyl
UCP-1
K hiu
Human prostatic carcinoma
Ung th tin lit tuyn ngi
Human Lung Carcinoma
Ung th phi ngi
Minimum Inhibitory Concentration Nng c ch ti thiu, hay
nng kim khun ti thiu
Nitric oxide synthases
Cc enzyme tng hp nitric
oxide
Optical density
Mt quang hc
Rhamnopyranoside
Reactive oxygen species
Cc gc t do xy ha
Rhabdo sarcoma
Ung th mng tim
Reserve phase C-18
Silica gel pha o RP-18
Prostaglandin E2
C tc dng gin mch trc tip,
gin c trn
Trichloracetic acid
Trichloracetic acid
Yu t chuyn dng tng trng
Transforming growth factor
kim sot s tng sinh, bit
ha t bo
Thin layer chromatography
Sc k lp mng
Tetramethylsilane
Tumor necrosis factor
Yu t hoi t khi u
Enzyme tryptophan hydroxylase
Enzyme thy phn tryptophan
Scavenging capacity
Kh nng by cc gc t do
Human colon adenocarcinoma cell Ung th tuyn i trng ngi
line
Xylopyranoside
Uncoupling protein-1
Protein tch cp -1
vii
DANH MC BNG
Bng 1. Cc hp cht alkaloid c phn lp t mt s loi ca chi Tetradium .......7
Bng 2. Cc hp cht triterpenoid phn lp t mt s loi ca chi Tetradium.........10
Bng 3. Cc hp cht limonoid c phn lp t mt s loi ca chi Tetradium ....12
Bng 4. Cc hp cht flavonoid c phn lp t mt s loi ca chi Tetradium ...13
Bng 5. Cc hp cht coumarin c phn lp t mt s loi ca chi Tetradium ...14
Bng 6. Cc hp cht benzenoid c phn lp t cy du du l nhn ..................15
Bng 7. Cc cc hp cht sterol c phn lp t mt s loi ca chi Tetradium ...16
Bng 8. S liu ph NMR ca TG1 v hp cht tham kho ....................................53
Bng 9. S liu ph NMR ca TG2 v hp cht tham kho ....................................59
Bng 10. S liu ph NMR ca TG3 v hp cht tham kho ..................................66
Bng 13. S liu ph NMR ca TG6 v hp cht tham kho .................................73
Bng 16. S liu ph NMR ca TG9 v hp cht tham kho .................................84
Bng 17. S liu ph NMR ca TG10 v hp cht tham kho ................................86
Bng 22. S liu ph NMR ca TG15 v hp cht tham kho ..............................105
Bng 25. S liu ph NMR ca TG18 v hp cht tham kho. .............................111
viii

Bng 30. S liu ph NMR ca TG23 v hp cht tham kho .............................123
Bng 33. S liu ph NMR ca TG26 v hp cht tham kho .............................127
Bng 34. Thng k hp cht phn lp c t cc b phn cy du du l nhn ..130
Bng 35. Kt qu xc nh hot tnh gy c t bo in vitro ..................................131
Bng 36. Hot tnh khng lao trn chng M. bovis v M. smegmatis .....................133
Bng 37. Kt qu xc nh hot tnh chng oxi ha ...............................................134
ix
DANH MC HNH
Hnh 1. Mu thc vt v mu tiu bn kh ca cy du du l nhn........................30
Hnh 2. S phn lp cc hp cht t mu l cy du du l nhn........................40
Hnh 3. S phn lp cc hp cht t mu v cy du du l nhn.......................43
Hnh 4. Cu trc v cc tng tc HMBC chnh ca hp cht TG1 ........................51
Hnh 5. Ph HR-ESI-MS ca TG1. ..........................................................................51
Hnh 6. Ph 1H-NMR ca TG1.................................................................................54
Hnh 7. Ph 1H-NMR gin (a) ca TG1. ..................................................................54
Hnh 8. Ph 1H-NMR gin (b) ca TG1. ..................................................................55
Hnh 9. Ph 13C-NMR ca TG1. ..............................................................................55
Hnh 10. Ph DEPT ca TG1. ..................................................................................56
Hnh 11. Ph HSQC ca TG1...................................................................................56
Hnh 12. Ph HMBC ca TG1. ................................................................................57
Hnh 13. Sc k ca cc dn xut TMS ca D-glucose, L-Glucose v TG1. ......57
Hnh 14. Cu trc ha hc v cc tng tc HMBC chnh ca TG2. ......................58
Hnh 15. Ph HR-ESI-MS ca hp cht TG2. .........................................................60
Hnh 16. Ph 1H-NMR ca TG2...............................................................................61
Hnh 17. Ph 1H-NMR gin ca TG2.......................................................................61
Hnh 18. Ph 13C-NMR ca TG2. ............................................................................62
Hnh 19. Ph DEPT ca TG2. ..................................................................................62
Hnh 20. Ph HSQC ca TG2...................................................................................63
Hnh 21. Ph HMBC ca TG2. ................................................................................63
Hnh 24. Cu trc ho hc v cc tng tc HMBC chnh ca TG5. ......................68
Hnh 25. Ph 1H-NMR ca TG5...............................................................................69
Hnh 27. Ph 13C-NMR ca TG5. ............................................................................70
Hnh 28. Ph DEPT ca TG5. ..................................................................................71
Hnh 29. Ph HSQC ca TG5...................................................................................71
Hnh 30. Ph HMBC ca TG5. ................................................................................72
x

Hnh 33. Ph 1H-NMR ca TG7...............................................................................76
Hnh 35. Ph 13C-NMR ca TG7. ............................................................................77
Hnh 36. Ph DEPT ca TG7. ..................................................................................78
Hnh 37. Ph HSQC ca TG7...................................................................................78
Hnh 38. Ph HMBC ca TG7. ................................................................................79
Hnh 40. Ph 1H-NMR ca TG8...............................................................................80
Hnh 41. Ph 13C-NMR ca TG8. ............................................................................80
Hnh 42. Ph 1H-NMR gin ca TG8. .....................................................................81
Hnh 43. Ph HSQC ca TG8...................................................................................81
Hnh 44. Ph HMBC ca TG8. ................................................................................82
Hnh 45. Cu trc ha hc ca hp cht TG9. .........................................................83
Hnh 46. Cu trc ha hc v cc tng tc HMBC chnh ca TG10. ....................85
Hnh 47. Ph 1H-NMR ca TG10.............................................................................87
Hnh 48. Ph 1H-NMR gin ca TG10.....................................................................87
Hnh 49. Ph 13C-NMR ca TG10. ..........................................................................88
Hnh 50. Ph DEPT ca TG10. ................................................................................88
Hnh 51. Ph HSQC ca TG10. ...............................................................................89
Hnh 52. Ph HMBC ca TG10. ..............................................................................89
Hnh 54. Ph 1H-NMR ca TG11. ...........................................................................92
Hnh 55. Ph 1H-NMR gin ca TG11. ...................................................................92
Hnh 56. Ph 13C-NMR ca TG11. .........................................................................93
Hnh 57. Ph DEPT ca TG11. ................................................................................93
Hnh 58. Ph HSQC ca TG11. ...............................................................................94
Hnh 59. Ph HMBC ca TG11. ..............................................................................94
Hnh 62. Cu trc v cc tng tc HMBC chnh ca TG14. ..................................98
xi
Hnh 63. Ph 1H-NMR ca TG14...........................................................................100

Hnh 64. Ph gin 1H-NMR ca TG14 (a). ............................................................101
Hnh 65. Ph gin 1H-NMR ca TG14 (b) .............................................................101
Hnh 66. Ph 13C-NMR ca TG14. ........................................................................102
Hnh 67. Ph DEPT ca TG14. ..............................................................................102
Hnh 68. Ph HSQC ca TG14. .............................................................................103
Hnh 69. Ph HMBC ca TG14. ............................................................................103
Hnh 70. Cu trc ha hc v cc tng tc HMBC chnh ca TG15. ..................104
Hnh 71. Cu trc ha hc ca TG16. ....................................................................105
Hnh 72. Cu trc ha hc ca hp cht TG17. .....................................................106
Hnh 73. Ph 1H-NMR ca TG17...........................................................................108
Hnh 74. Ph 1H-NMR gin ca TG17. .................................................................108
Hnh 75. Ph 13C-NMR ca TG17. ........................................................................109
Hnh 76. Ph DEPT ca TG17. ..............................................................................109
Hnh 77. Cu trc v cc tng tc HMBC chnh ca TG18. ................................110
Hnh 78. Ph HR-ESI-MS ca TG18. ....................................................................112
Hnh 79. Ph 1H-NMR ca TG18...........................................................................112
Hnh 80. Ph 1H-NMR gin ca TG18...................................................................113
Hnh 81. Ph 13C-NMR ca TG18. ........................................................................113
Hnh 82. Ph DEPT ca TG18. ..............................................................................114
Hnh 83. Ph HSQC ca TG18. .............................................................................114
Hnh 84. Ph HMBC ca TG18. ............................................................................115
Hnh 88. Cu trc v cc tng tc HMBC chnh ca TG22. ................................120
Hnh 90. Cu trc ha hc ca hp cht TG24. .....................................................123
Hnh 92. Cu trc ha hc ca TG26 .....................................................................127
Hnh 93. Cc hp cht c phn lp t cy du du l nhn. ...............................129
Hnh 94. Kt qu th hot tnh cc hp cht phn lp t cy du du l nhn. ......136
xii
M U
Th gii thc vt l ngun ti nguyn phong ph v v cng qu gi v
nhng hp cht thin nhin c hot tnh sinh hc. Khng ch cc nc phng ng
m cc nc phng ty cng tiu th mt lng rt ln dc liu. Theo thng k,
cc nc c nn cng nghip pht trin, mt phn t s thuc k trong cc n
u c cha hot cht c ngun gc t tho mc. Nhiu hp cht th cp c hot
tnh sinh hc tt c phn lp v a vo s dng vi mc ch cha bnh. Xu
hng i su nghin cu v tm kim cc hp cht t nhin c hot tnh sinh hc
cao t cc loi thc vt lm dc phm cha bnh ang ngy cng thu ht c s
quan tm ca cc nh khoa hc bi u im ca chng l c tnh thp, d hp thu
v chuyn ha trong c th hn so vi cc dc phm tng hp.
Vit Nam l mt nc nm trong vng kh hu nhit i gi ma nn c h
thc vt a dng v phong ph. Theo c tnh, nc ta c khong gn 13000 loi
thc vt bc cao trong c khong hn 4000 loi c s dng lm thuc. Vic s
dng ngun ti nguyn phng, cha bnh v nng cao sc kho cho con
ngi c mt qu trnh lch s hng nghn nm v ngy cng tr nn quan trng.
Ngoi s a dng v thnh phn chng loi, ngun dc liu Vit Nam cn
c gi tr to ln ch chng c s dng rng ri trong cng ng cha nhiu
loi bnh khc nhau. Cc cy thuc c s dng di hnh thc c v hay phi
hp vi nhau to nn cc bi thuc qu gi. Ngoi ra, hng trm cy thuc c
khoa hc y - dc hin i chng minh v gi tr cha bnh ca chng.
Cy du du l nhn (Tetradium glabrifolium (Benth.) Hartl.) l mt cy
thuc thuc h Cam qut (Rutaceae) thng c s dng tr mt s bnh nh: tr
tn thng do ng, gy xng, thp khp. Thn v l cy dng tr vim thn, ph
thng, dng ngoi cha chn thng, nga, eczema. L cy c dng nu nc
tm cho b hoc nu nc c ra vt thng, tm gh l. L cy cn c
gi chng vi gim p chng sng, tc tia sa. Qu v v c dng sc ung
li tiu hoc i tiu, cha kit l, to bn v thp khp... Cc nghin cu v
thnh phn ha hc ca loi ny ch ra s c mt ca cc lp cht alkaloid,
1
triterpenoid, benzenoid v coumarin... Nhiu hp cht trong s th hin nhiu

hot tnh tt nh evomeliaefolin, rutaevinexic acid, isolimonexic acid.
Nhm mc ch nghin cu lm r thnh phn ha hc v hot tnh sinh hc
ca cy du du l nhn (Tetradium glabrifolium), chng ti la chn ti:
Nghin cu thnh phn ha hc v hot tnh sinh hc cy du du l nhn
Tetradium glabrifolium (Benth.) Hartl..
Mc tiu ca lun n: Nghin cu lm r thnh phn ho hc ch yu

ca cy du du l nhn nhm tm kim cc hp cht c hot tnh sinh hc, lm c
s khoa hc cho nhng nghin cu tip theo to ra sn phm chm sc sc khe
cng ng v gp phn gii thch c tc dng cha bnh ca v thuc ny.
Ni dung lun n bao gm:

1. Phn lp cc hp cht t l v v thn cy du du l nhn bng cc phng
php sc k;
2. Xc nh cu trc ho hc cc hp cht phn lp c bng cc phng php
vt l v ha hc;
3. nh gi hot tnh gy c t bo, hot tnh khng lao, hot tnh chng oxi
ha v hot tnh khng vi sinh vt ca cc hp cht phn lp c.
CHNG 1
TNG QUAN TI LIU
1.1. GII THIU V CHI TETRADIUM
1.1.1. c im thc vt chi Tetradium
H Cam qut (Rutaceae) hay cn gi l h Cu l hng l mt h thc vt
trong b B Hn (Sapindales) vi khong 161 chi vi hn 2070 loi, phn b ch
yu vng nhit i v n i m, c bit l Nam Phi, chu c v chu [1].
Chi Tetradium l mt chi trong h Cam qut (Rutaceae), phn b t vng ni
Himalaya n vng nhit i ng Nam . Trong cc ti liu c, cc loi ca chi
Tetradium thng b xp vo chi Euodia (nhiu ti liu vit l Evodia), nhng bt
u t nm 1981, chi Euodia c chia thnh 3 chi: Tetradium, Euodia v
Melicope [1, 2].
Theo phn loi thc vt hc, chi Tetradium bao gm 12 loi, nhng trong s
ny mi ch c 8 loi c chp nhn tn:
-
Tetradium austrosinense (Handel-Mazzetti) T. G. Hartley, 1981;
Tetradium calcicolum (Chun ex C. C. Huang) T. G. Hartley, 1981;
Tetradium daniellii (Bennett) T. G. Hartley, 1981;
Tetradium fraxinifolium (Hooker) T. G. Hartley, 1981;
Tetradium glabrifolium (Champion ex Bentham) T. G. Hartley, 1981;
Tetradium ruticarpum (A. Jussieu) T. G. Hartley, 1981;
Tetradium sambucinum (Blume) T.G. Hartley, 1981;
Tetradium trichotomum (Loureiro) Fl. Cochinch, 1790.
Cc loi trong chi Tetradium thng c thn bi hoc thn g, l di khong

14-38 cm hnh lng chim hoc hnh elip, khng c rng ca, sng bng mu xanh
m trn, nht mu v c lng bn di. Hoa gm cc bng nh, n tnh, trong
cc cm, mu trng vi bao phn mu vng. Cnh hoa mu xanh l cy, vng hoc
trng. Chm hoa t 8-16 cm, phn nhnh cui cc cnh nh. Hoa c mi thm v
xut hin vo gia n cui ma h, d nhn thy, rt hp dn vi ong. Tri cy
mu hng hoc gn nh mu en, c m trong cm ln v sc s. Ht mu en sng
bng, qu chn vo cui ma h v tn ti qua ma ng [1, 2].
3
1.1.2 Cc nghin cu v thnh phn ha hc ca chi Tetradium

Hin nay, theo thng k, trong 8 loi c cng nhn tn ca chi Tetradium,
mi c 5 loi c cng b v thnh phn ha hc, bao gm: T. daniellii, T.
glabrifolium, T. ruticarpum, T. sambucinum v T. trichotomum. Cc nghin cu v
thnh phn ha hc v chi Tetradium cho thy s c mt ca nhiu lp cht, nh:
alkaloid, triterpenoid, flavonoid, coumarin, benzenoid, amide, tannin, sterol ...
Nm 1988, cc nh khoa hc Nht Bn phn lp t loi Evodia
rutaecarpa (tn khc ca loi T. ruticarpum) hai mi hp cht trong c chn
hp cht mi gm bn limonoid: 12-hydroxylimonin (73), 12-hydroxyevodol
(65), 6-acetoxy-5-epilimonin (70) v 6-acetoxy-5-epilimonin (71); nm
quinolone alkaloid: 1-methyl-2-[(Z)-6-undecyl]-4(1H)-quinolone (37), 1-methyl-2[(Z)-6-pentadecenyI]-4(1H)-quinolone (38), 1-methyl-2-[(Z)-10-pentadecenyl] -4(1H)quinolone (40), 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone
(41), 1-
methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone (42) v by limonoid

bit l: evodol (66), rutaevine (67), rutaevine acetate(68), graucin A (69), limonin
(72), obacunone (78) v jangomolide (79); bn hp cht quinolone alkaloid bit:
1-methy1-2-undecyl-4(1H)-quinolone (28), dihydroevocarpine (31), 1-methyl-2pentadecyl-4(1H)-quinolone (33) v evocarpine (39) [3].
Nm 1990, Abdul Quader v ng nghip ti Khoa Dc, i hc
Strathclyde, Vng quc Anh phn lp t thn cy v v cy T. trichotomum hai
alkaloid l: -allocryptopine (6), dictamnine (17) v ba limonoid l: calodendrolide
(56), limonexic acid (64) v limonin (72) [4].
Nm 1991, Miyake v cng s ti Vin nghin cu Sinh hc nng nghip
Wakayama, Momoyama, Nht Bn phn lp c ba hp cht limonoid mi t
qu loi T. rutacarpum, gm: limonin 17-D-glucopyranoside (74), limonin
diosphenol 17-O--D-glucopyranoside (75), 6-hydroxy-5-epilimonin 17-O--Dglucopyranoside (76) v ba hp cht limonoid bit l: limonin diosphenol (62),
rutaevine (67) v limonin (72) [5].
Nm 2002, nhm nghin cu ca GS. Trn Vn Sung v cng s ti Vin
Ha hc, Vin Hn lm Khoa hc v Cng ngh Vit Nam phn lp c 3 hp
4
cht alkaloid t cy T ch ba (T. trichotomum) l: rutaecarpine (7), evodiamine

(10) v nauclefin (13) [6].
Nm 2003, Stevenson v cc ng nghip thuc Trung tm Nghin cu quc
t Jealott's Hill, Vng quc Anh phn lp t phn dch chit qu sy kh ca
loi T. daniellii mt furanocoumarin mi l 5-(6-hydroxy-3,7-dimethylocta-2,7dienyloxy) psoralen (97) v su hp cht furanocoumarin bit l xanthotoxin
(94), bergapten (95), isopimpinellin (96), 5-(7-hydroxy-3,7-dimethylocta-2,5dienyloxy) psoralen (98), 5-geranyloxypsoralen (99) v 8-geranyloxypsoralen
(100). Cc hp cht ny u th hin hot tnh tt ngn chn s pht trin u trng
Spodoptera littoralis v Heliothis virescens [7].
Nm 2006, nhm nghin cu ca Komala Ismiarni ti trng i hc Putra,
Malaysia nghin cu thnh phn ha hc l loi T. sambucinum, phn lp
c bn hp cht, bao gm: decarine (1), rutaecarpine (7), aurantiamide acetate
(15) v umbelliferone (7-hydroxycoumarin) (92) [8].
Nm 2007, cc nh khoa hc Hn Quc phn lp t dch chit qu ca
loi T. ruticarpum su hp cht quinolone alkaloid gm: 1-methyl-2-nonyl-4(1H)quinolone (27), 1-methyl-2-undecyl-4(1H)-quinolone (29), dihydroevocarpine (31),
1-methyl-2-[(Z)-6-undecenyl]-4(1H)-quinolone (37), evocarpine (39) v 1-methyl2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone (42) [9].
Vo nm 2010, Tzu-Ying Wang v ng nghip ti i hc Y khoa i
Trung, i Loan phn lp t qu ca loi T. ruticarpum mt quinolone alkaloid
mi l: 1-[(6Z,9Z)- 6,9-pentadecadienyl]-4(1H)-quinolin (42) v mi mt hp
cht bit gm su hp cht alkaloid: rutaecarpine (7), evodiamine (10), 14formyldihydrorutaecarpine (11), skimmianine (20), dihydroevocarpine (31) v
evocarpine (39); mt hp cht limoloid l evodol (66); bn hp cht sterol l: sitosterol (121), stigmasterol (123), 3-hydroxystigmast-5-en-7-one (124) v 3hydroxystigmasta-5,22-dien-7-one (125) [10].
Nm 2012, mt nhm cc nh khoa hc thuc Khoa Thuc t nhin v M
phng sinh hc, Khoa Dc, i hc Bc Kinh, Trung Quc phn lp t qu ca
loi T. ruticarpum c mi by hp cht, trong c ba quinolone alkaloid mi
5
l 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (43), 1-methyl-2[(Z)-4-nonenyl]-4(1H)-quinolone (34) v 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]

-4(1H)-quinolone (45); mt hp cht mi phn lp t t nhin l 1-methyl-2-[(E)1-undecenyl]-4(1H)-quinolone (46) cng vi mi ba hp cht quinolone alkaloid
bit l: 1-methyl-2-nonyl-4(1H)-quinolone (27), 1-methyl-2-decyl-4(1H)quinolone (28), 1-methyl-2-undecyl-4(1H)-quinolone (29), 1-methyl-2-dodecyl4(1H)-quinolone (30), dihydroevocarpine (31), 1-methyl-2-tetradecyl-4(1H)quinolone (32), 1-methyl-2-pentadecyl-4(1H)-quinolone (33), 1-methyl-2-[(Z)-6undecenyl-4(1H)-quinolone (37), 1-methyl-2-[(Z)-6-pentadecenyl]-4(1H)-quinolone
(38), evocarpine (39), 1-methyl-2-[(Z)-10-pentadecenyl]-4(1H)-quinolone (40), 1methyl-2-[(4Z,7Z)-
4,7-tridecadienyl]-4(1H)-quinolone
(41),
1-methyl-2-
[(6Z,9Z)- 6,9-pentadecadienyl]-4(1H)-quinolone (42). Tuy nhin, 43 l mt hp

cht khng n nh trong mi trng t nhin nn bin i thnh mt hp cht nhn
to mi l 1-methyl-2-[7-cacbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (44) [11].
Gn y nht, nm 2013, cc nh khoa hc Trung Quc nghin cu dch
chit t qu loi T. ruticarpum c thu thp tnh Chit Giang (Trung Quc),
phn lp c hai mi alkaloid trong c chn hp cht mi, gm nm
quinolone alkaloid mi l euocarpine A-E (47-51) v bn hp cht mi l: 1methyl- 2-ethyl-4(1H)-quinolone (23), 1-methyl-2-octyl-4(1H)- quinolone (26), 1methyl-2-[(Z)-5-dodecenyl]-4(1H)-quinolone (35), 1-methyl-2-[(Z)-5-pentadecenyl]
-4(1H)-quinolone (36), cng mi hp cht bit l: 1-methyl-2-pentyl-4-(1H)quinolone (24), 1-methyl- 2-heptyl-4(1H)-quinolone (25), 1-methyl-2-nonyl-4(1H)quinolone (27), 1-methyl-2-decyl-4(1H)-quinolone (28), 1-methyl-2-undecyl4(1H)-quinolone (29), 1-methyl-2-dodecyl-4-(1H)-quinolone (30), dihydroevocarpine
(31), 1-methyl-2-tetradecy-4-(1H)-quinolone (32), 1-methyl-2-pentadecenyl-4(1H)quinolone (33), evocarpine (39) v 1-methyl-2-[(6Z, 9Z)-6, 9-pentadecadienyl]4(1H)-quinolone (42) [12].
Da theo vic phn loi cc lp hp cht t nhin, 135 hp cht c phn
lp t cc loi thuc chi Tetradium c thng k theo cc lp cht sau y:
6
1.1.2.1. Cc hp cht alkaloid

Cc cng b nghin cu v thnh phn ha hc ca chi Tetradium cho thy,
hu ht cc loi ca chi ny u cha cc hp cht alkaloid. Cho n hin ti, tng
cng c 53 hp cht alkaloid c phn lp t chi ny (Bng 1).
Bng 1. Cc hp cht alkaloid c phn lp t mt s loi ca chi Tetradium
KH
Tn cht
Loi
TLTK
Decarine
Norchelerythrine
Bocconoline
T. glabrifolium,
[8, 109]
T. sambucinum
T. glabrifolium [109]
6-Acetonyl-5,6-dihydrochelerythrine
T. glabrifolium
[109]
Oxychelerythrine
T. glabrifolium
[109]
-Allocryptopine
[4]
Rutaecarpine
8
9
1-Hydroxyrutaecarpine
Hortiacine
11 14-Formyldihydrorutaecarpine
T. trichotomum
T. glabrifolium,
T. trichotomum,
T. sambucinum,
T. ruticarpum
T. glabrifolium
T. glabrifolium
T. trichotomum,
T. ruticarpum
T. ruticarpum
[10]
12 Hydroxyevodiamine (rhetsinine)
T. ruticarpum
[58, 86]
13 Nauclefin
T. trichotomum [6]
14 Dehydroevodiamine
T. ruticarpum
15 Aurantiamide acetate
T. sambucinum [8]
16 Arnottianamide
T.glabrifolium [109, 110]

T. glabrifolium,
[4, 109]
T. trichotomum
10 Evodiamine
17 Dictamnine
18 Robustine
19 -Fagarine
[6, 8, 10, 58, 109]

[110]
[109]
[5, 10, 58]
[58, 86]
21 Methyl--carboline-1-carboxylate
T. glabrifolium,
[10, 109]
T. ruticarpum
22 Strychnocarpin
T. glabrifolium
20 Skimmianine
[111]
23 1-Methyl-2-ethyl-4(1H)-quinolone
T. ruticarpum
[12]
24 1-Methyl-2-pentyl-4(1H)-quinolone
T. ruticarpum
[12]
25 1-Methyl-2- heptyl-4(1H)- quinolone
T. ruticarpum
[12]
26 1-Methyl-2-octyl-4(1H)- quinolone
T. ruticarpum
[12]
27 1-Methyl-2-nonyl-4(1H)-quinolone
T. ruticarpum
[9, 11, 12]
28 1-Methyl-2-decyl-4(1H)-quinolone
T. ruticarpum
[11, 12]
29 1-Methyl-2- undecyl-4(1H)-quinolone T. ruticarpum
[3, 9, 11, 12]
30 1-Methyl-2-dodecyl-4(1H)-quinolone
T. ruticarpum
[11, 12]
31 Dihydroevocarpine
T. ruticarpum
[3, 9, 10, 11, 12]
32 1-Methyl-2-tetradecyl-4(1H)-quinolone
1-Methyl-2-pentadecenyl-4(1H)33
quinolone
1-Methyl-2-[(Z)-4-nonenyl]-4(1H)34
quinolone
1-Methyl- 2-[(Z)-5-dodecenyl]-4(1H)35
quinolone
1-Methyl-2-[(Z)-5-pentadecenyl]36
4(1H)-quinolone
1-Methyl-2-[(Z)-6-undecenyl-4(1H)37
quinolone
4(1H)-quinolone
1-Methyl-2-[(Z)-8-tridecenyl]-4(1H)39
quinolinone (evocarpine)
4(1H)-quinolone
1-Methyl-2-[(4Z,7Z)- 4,741
tridecadienyl]-4(1H)- quinolone
1-Methyl-2-[(6Z, 9Z)- 6,942
pentadecadienyl] -4(1H)-quinolone
1-Methyl-2-[7-hydroxy-(E)-943
tridecenyl]-4(1H)-quinolone
1-Methyl-2- [7-cacbonyl -(E)- 9 44
tridecenyl ]-4(1H)-quinolone
1-Methyl-2-[(1E,5Z)- undecadienyl]45
4(1H)-quinolone
1-Methyl-2-[(E)-1-undecenyl]-4(1H)46
quinolone
47 Euocarpine A
T. ruticarpum
[11, 12]
T. ruticarpum
[3, 11, 12]
T. ruticarpum
[11]
T. ruticarpum
[12]
T. ruticarpum
[12]
T. ruticarpum
[3, 9, 11]
T. ruticarpum
[3, 11]
T. ruticarpum
[3, 9, 10, 11, 12]
T. ruticarpum
[3, 11]
T. ruticarpum
[3, 11]
T. ruticarpum
[3, 9, 10, 11, 12]
T. ruticarpum
[11]
T. ruticarpum
[11]
T. ruticarpum
[11]
T. ruticarpum
[11]
T. ruticarpum
[12]
T. ruticarpum
[12]
48 Euocarpine B
8
49 Euocarpine C
T. ruticarpum
[12]
50 Euocarpine D
T. ruticarpum
[12]
51 Euocarpine E
[12]
T. ruticarpum
T. glabrifolium,
[9, 109]
T. ruticarpum
52 4-Methoxy-1-methyl-2-quinolone
53 Evomeliaefolin
O
O
O
H3CO
R
OCH3
CH3
R1
H3CO
R
OH
OCH3
1
2
R1
H
H
=O
3
4
5
R1
R2
N
H3CO
CH3
OCH3
R2
CH2OH
CH2COCH3
-
R1
O
N
H
N
H
7
8
9
N
H
N
R2
R2
R1
H
H
OCH3
13
R2
H
OH
H
R1
H
H
OH
10
11
12
R2
CH3
CHO
CH3
O
H3CO
O
O
N
H
H
N
N
H
H3C
H3C
H
O
H3CO
OCOCH3
OH
14
16
15
R2
R1
OCH3
R1
17
18
19
20
R2
H
H
H
OH
H
OCH3
OCH3 OCH3
N
N
H
COOCH3
21
N
H
22
CH3
R
O
27
R
40
1'
29
R
N
CH3
1'
42
30
31
33
23
1'
25
35
1'
45
1'
5'
1'
5'
6'
1'
46
1'
5'
5'
47
6'
1'
48
6'
6'
37
7'
6'
8'
7'
49
8'
O
8'
9'
50
1'
OCH3
OH
51
1'
6'
7'
39
7'
O O
5'
38
9'
7'
36
26
9'
OH
1'
44
34
24
10'
9'
6'
1'
7'
4'
1'
8'
7'
5'
43
32
R
4'
41
28
11'
10'
1'
C9H19
CH3
52
CH3
H3CO
9'
8'
10'
OCH3
OH
N
H
OCH3
53
1.1.2.2. Cc hp cht triterpenoid

Theo cc nghin cu, c tm hp cht triterpenoid c phn lp t hai
loi T. glabrifolium v T. trichotomum ca chi Tetradium [4, 109, 111] Bng 2.
Bng 2. Cc hp cht triterpenoid c phn lp t mt s loi ca chi Tetradium
KH
Tn cht
Loi
TLTK
54
Squalene
T. glabrifolium
[111]
55
Atractylenolide III
T. glabrifolium
[109]
56
Calodendrolide
T. trichotomum
[4]
57
-Amyrin acetate
T. glabrifolium
[111]
58
Lupeol
T. glabrifolium
[109]
59
Taraxeron
T. glabrifolium
[111]
60
epi-Taraxerol
T. glabrifolium
[111]
61
Taraxerol
T. glabrifolium
[111]
10
O
OH
O
O
55
54
56
R1
R2
H3CCOO
HO
59
60
61
58
57
R2
OH
H
R1
=O
H
OH
1.1.2.3. Cc hp cht limonoid

Limonoid l cc hp cht tetranortriterpenoid gy ra v ng, cay trong ht
tri cy cc loi trong h Cam qut. Cc hp cht ny c cc hot tnh sinh hc c
trng nh: khng khun, khng nm, chng st rt, chng ung th, khng virus ...
thm vo chng c tc dng tr su, dit v kim sot s tng trng cn trng.
Hin nay, c hng trm limonoid c phn lp t cc loi khc nhau, nhng
ch yu l cc loi trong h Cam qut v h Xoan. Cc hp cht limonoid c khung
hoc c dn xut t khung 4,4,8-trimethyl-17-furanyl steroid. Tt c cc
limonoid c phn lp t h Cam qut u c mt vng furan gn vi khung
chnh ti C-17 v cc nhm th c cha oxiti C-3, C-4, C-7 v C-16 [13].
Theo cc cng trnh cng b, c mi tm hp cht limonoid c phn
lp t cc loi ca chi Tetradium [3, 4, 5, 109, 110, 111]:
O
O
O
O O
O
OH
64
63
11
OH
62
O
O
HO
O
O
HO
65
66
R
OH
H
Bng 3. Cc hp cht limonoid c phn lp t mt s loi ca chi Tetradium

KH
Tn cht
Loi
TLTK
62
Limonin diosphenol
T. rutacarpum
[5]
63
Limonexic acid
T. trichotomum
[4]
64
Isolimonexic acid
T. glabrifolium
[110]
65
12-Hydroxyevodol
T. glabrifolium
[3], [109]
66
Evodol
67
Rutaevine
68
69
70
Rutaevine acetate
Graucin A
6-Acetoxy-5-epilimonin
T. glabrifolium
T. glabrifolium
T. rutacarpum
T. rutacarpum
T. glabrifolium
T. rutacarpum
[3], [109]
[3], [5], [58],
[109]
[3]
[3], [109]
[3]
71
6-Acetoxy-5-epilimonin
[3], [109]
72
Limonin
73
12-Hydroxylimonin
T. glabrifolium
T.glabrifolium,
T. trichotomum,
T. rutacarpum
T. rutacarpum
[3]
74
T. rutacarpum
[5]
T. rutacarpum
[5]
T. rutacarpum
[110]
77
Limonin 17-O--D- glucopyranoside

Limonin diosphenol 17--Dglucopyranoside
6-Hydroxy-5-epilimonin 17-Dglucopyranoside
Rutaevinexic acid (limonoic acid)
[110]
78
Obacunone
T. glabrifolium
T. rutacarpum
[3]
79
Jangomolide
T. rutacarpum
[3]
75
76
R1
R2
67
68
69
OGlc
O
O
R2
H
OH
H OCOCH3
OH
OH
R1
70
71
72
73
H
H
H
OH
OGlc
COOH
O
COOH
O
R2
R1
O
O
R1
[3], [4], [5],

[109], [110]
O
OH
R2
74
OCOCH3
OCOCH3
H
H
12
75
O
OGlc
COOH
O
O
O
OH
COOH
O
O
OH
OH
76
79
78
77
1.1.2.4. Cc hp cht flavonoid

Cc nghin cu v thnh phn ha hc trong chi Tetradium cho thy, c chn
hp cht flavonoid c phn lp t hai loi T.glabrifolium v T. rutacarpum:
OGlc
OH
OH
OH
O
HO
HO
R2 HO
OR1
O
OH
OH
81 Xyl
82 Gal
OH
OH
R2
H
OH
R1
80
O
OH
HO
83
OH
OR
OH
O
HO
GlcO
HO
OGlc(16)Rha
OH
O
OH
O
OH
O
OH
84
85
R
H
OH
HOH2C
86
OH
87
88
R
Glc
H
Bng 4. Cc hp cht flavonoid c phn lp t mt s loi ca chi Tetradium

KH
80
Tn cht
Liquiritin
Loi
T. glabrifolium
TLTK
[111]
81
Kaempferol-3-O--D-xylopyranoside
T. glabrifolium
[111]
82
Hyperoside (hyperin)
T. rutacarpum
[58]
83
Quercetin-3-O--L-arabinopyranoside
T. rutacarpum
84
Nicotiflorin
T. glabrifolium
[58]
[111]
85
Rutin
T. glabrifolium
[111]
86
Juglanin
T. glabrifolium
[111]
87
Evodioside B
T. glabrifolium
[111]
88
Epimedoside C
T. glabrifolium
[111]
13
1.1.2.5. Cc hp cht coumarin

Coumarin l mt lp cht thin nhin c tc dng dc l cao, th hin nhiu
hot tnh hu ch, nh: khng nm, chng khi u, chng ng mu, khng virut
HIV, tr bnh cao huyt p, chng long xng thng phn lp c trong cc
loi thuc h u (Fabaceae), Hoa tn (Apiaceae), Cam qut (Rutaceae) Cc hp
cht coumarin c tm thy trong hu ht cc loi ca chi Tetradium. Theo cc ti
liu thng bo [7, 8, 109, 111] c mi hai hp cht coumarin c phn lp:
R1
R2 O
O
R3
89
90
91
92
93
R1
H
OCH3
OCH3
H
OCH3
R2
Glc
Glc
H
H
H
94
95
96
97
98
99
100
R1
H
OCH3
OCH3
(A)
(B)
(C)
H
R2
OCH3
H
OCH3
H
H
H
(D)
R1
( A)
O
OH OH
(B)
O
O
O
R2
( C)
( D)
O
O
R3
H
H
Glc
H
H
Bng 5. Cc hp cht coumarin c phn lp t mt s loi ca chi Tetradium

KH
Tn cht
Loi
TLTK
89
Skimmin
T. glabrifolium
[111]
90
Isofraxoside
T. glabrifolium
[111]
91
T. glabrifolium
T. glabrifolium;
T. sambucinum
T. glabrifolium
[111]
93
Fraxin
Umbelliferone
(7-hydroxycoumarin)
Scopoletin
94
Xanthotoxin
T. daniellii
95
Bergapten
T. daniellii
[7]
[7]
96
T. daniellii
[7]
99
Isopimpinellin
5-(6-Hydroxy-3,7-dimethylocta-2,7dienyloxy) psoralen
5-(7-Hydroxy-3,7-dimethylocta-2,5dienyloxy)psoralen
5-Geranyloxypsoralen
T. daniellii
[7]
100
8-Geranyloxypsoralen
T. daniellii
[7]
92
97
98
14
T. daniellii
T. daniellii
[8, 109, 111]

[111]
[7]
[7]
1.1.2.6. Cc hp cht benzenoid

Theo thng k t cc ti liu cng b, c hai mi hp cht benzenoid
trong chi Tetradium u phn lp t loi T.glabrifolium [109, 111]:
Bng 6. Cc hp cht benzenoid c phn lp t cy du du l nhn
KH
Hp cht
TLTK KH
101 p-Hydroxybenzaldehyde [109, 111
111]
102 p-Hydroxybenzoic acid [109, 112
111]
[111] 113
103 Protocatechuic acid
Hp cht
Methylglallate
TLTK
[111]
[109]
104 Methylparaben
[109]
Methyl-phydroxycinnamate
trans-4'-Hydroxy-3'methoxycinnamaldehyde
114 Evofolin C
105 Methylsyringat
[109]
115 Evofolin A
[109]
106 Syringaldehyde
[109]
116 Evofolin B
[109]
107 Vanillin
[109]
108 3,4,5-Trimethoxybenzyl
alcohol
109 Methylvanillate
[109]
[109]
117 -Hydroxypropioguaiacone [109]

[109]
118 2'-Hydroxy-4'methoxyacetophenone
[111]
119 -Glucogallin
110 Gallic acid
[111]
120 Methylchlorogenate
OR2
R1
R3
OCH3
(A)
CH3
(C)
[111]
(F)
CH3
OH
OH
(E)
(B)
(D)
[109]
CH2OH
[109]
CH3
OH
OCH3
R4
101
102
103
104
105
106
107
108
R1
H
H
OH
H
OCH3
OCH3
H
OCH3
R2
H
H
H
H
H
OCH3
H
CH3
R3
H
H
H
H
OCH3
OCH3
OCH3
OCH3
R4
CHO
COOH
COOH
COOCH3
COOCH3
CHO
CHO
CH2OH
15
109
110
111
112
113
114
115
116
R1
OCH3
OH
OH
H
OCH3
H
OCH3
OCH3
R2
H
H
H
H
H
(C)
H
H
R3
H
OH
OH
H
H
H
H
H
R4
COOCH3
COOH
COOCH3
(A)
(B)
(D)
(E)
(F)
OH
OCH3
OCH3
HO
OH
HO
OH
OH
OH
HO
GlcO
HO
OH
COOCH3
O
H 3C
117
O
OH
118
119
120
1.1.2.7. Cc hp cht sterol

C nm hp cht sterol c phn lp c t chi Tetradium [10, 109] gm:
RO
121
122
HO
HO
R
H
Glc
HO
125
124
123
Bng 7. Cc cc hp cht sterol c phn lp t mt s loi ca chi Tetradium

KH
Tn cht
121
-Sitosterol
122
Sitosteryl glucoside
Loi
T. glabrifolium,
T. ruticarpum
T. glabrifolium
TLTK
123
Stigmasterol
T. ruticarpum
[10]
124
3-Hydroxystigmast-5-en-7-one
T. ruticarpum
[10]
125
3-Hydroxystigmasta-5,22- dien-7-one
T. ruticarpum
[10]
[10, 109]
[109]
1.1.2.8. Cc hp cht khc

Ngoi ra, theo hai cng trnh ca Wu v cng s (H Quc gia Cheng Kung,
i Loan) t loi T. glabrifolium cn phn lp c nm hp cht amide:
hortiamide (126), cis-N-p-coumaroyltyramin (127), trans-N-p-coumaroyltyramin
(128), cis-N-feruloyltyramin (129), trans-N-feruloyltyramin (130) [109]; hai hp
cht tanin: corilagen (131), ellagic acid (132) [111]; mt hp cht ng: myo
inositol (133) [111]; mt hp cht lignan: (-)-matairesinol (134) [109] v mt hp
cht nucleosid: adenosine (135) [111]:
16
OH
OH
O
HO
O
NH
NH
O
NH
127
OH
126
128
HO
OCH3
HO
HO
OCH3
N
H
N
H
OH
129
HO
130
O
HO
OH
O
HO
O
HO
O
HO
OH
O
OH
OH
OH
OH
HO
O
O
HO
132
131
HO
OH
NH2
H3CO
OH
OH
HO
HO
O
OH
N
O
OH
OH
133
OH
OCH3
134
OH
OH
OH
135
Kt lun:
Theo cc nghin cu v thnh phn ha hc ca chi Tetradium trong cc loi
c cng b v thnh phn ha hc (T. daniellii, T. glabrifolium, T. ruticarpum,
T. sambucinum v T. trichotomum) phn lp c 135 hp cht, cho thy s c
mt rt a dng ca cc lp cht trong t nhin (12 lp cht), gm: 53 alkaloid, 8
triterpenoid, 18 limonoid, 9 flavonoid, 12 coumarin, 20 benzenoid, 5 amide, 2
tannin, 5 sterol, 1 ng, 1 hp cht lignan v 1 hp cht nucleoside.
17
1.1.3. Cc nghin cu v hot tnh sinh hc ca chi Tetradium

1.1.3.1. Tc dng khng ung th
Trong cc lp cht phn lp c t chi Tetradium, cc hp cht limonoid c
rt nhiu hot tnh th v. Gn y, nhiu cng trnh nghin cu chng minh
c rng cc limonoid th hin hot tnh vi cc mc khc nhau trn nhiu loi
t bo ung th nh: ung th phi, ung th i trng, ung th vm hng, ung th da,
ung th v v ung th d dy [14, 15, 16, 17, 18].
Mt s nghin cu chng minh rng, cc hp cht limonoid lm tng hot
enzyme glutathione S-transferace v quinine reductase l cc enzyme c tc
dng chuyn ha v loi tr tc hi ca nhiu tc nhn ha hc c hi, xc tc cho
qu trnh lin kt gia glutathione vi nhiu hp cht c kh nng gy ung th c i
lc in t trong t nhin. Hm lng cc enzyme ny tng tng quan vi kh
nng c ch ung th gy ra do cc tc nhn ha hc [19, 20].
Trong cc cng trnh nghin cu v bnh ung th vm hng trn chut
hamster, Miler v cc cng s cng chng minh c rng limonin (72) hot
ng nh mt tc nhn by, bt v ngn chn cc hp cht benzo[a]pyrene v cht
gy t bin khc trc khi chng gn vi cc t bo trong c th ng vt th
nghim. Limonin (72) c ch mnh 7, 12-dimethylbenzo[a]anfliracene l mt tc
nhn gy ra ung th vm hng v c tc dng ngn s hnh thnh ung th mt trc
ca d dy v ung th i trng trn chut thc nghim. Cc nghin cu ch ra rng
h vng trong nhn v nhm furan c trong limonoid l yu t quan trng trong
hot tnh chng ung th [21, 22, 23].
Nhm nghin cu ca Jie Yang chng minh evodiamine (10) c tc dng c
ch in vitro b chuyn i tn hiu v kch hot phin m 3 (STAT3) v khi u ca
cc t bo ung th biu m gan ngi HepG2 bng cch ngn chn phng thc tn
hiu STAT3 lin quan n s tn ti, pht trin, hnh thnh v c ch min dch ca
cc t bo ung th biu m t bo gan trn m hnh ng vt thc nghim [24].
Hp cht rutaecarpine (7) l mt trong nhng alkaloid gp phn th hin
nhiu hot tnh quan trng ca cc loi trong chi Tetradium. Cc nghin cu ca
nhm nghin cu Yang v cng s xc nh kh nng c ch s pht trin cc
18
dng t bo ung th (GI50) ca hp cht 7. C th dng t bo rut kt HT-29 (31,6

M), ung th phi A-549/ATCC (14,5 M), ung th bung trng OVCAR-4 (18,9
M) ung th v HS-578T (22,6 M) [25, 26].
Decarine (1) c phn lp t loi T. sambucinum th hin hot tnh c t
bo i vi dng t bo ung th c t cung HeLa (IC50 l 14,6 g/mL) [8].
Nm 2012, cc nh khoa hc Trung Quc phn lp c mi by hp
cht quinolone alkaloid t loi T. ruticarpum l: 27-34, 37-43, 45, 46. Cc hp cht
ny c nh gi hot tnh gy c t bo trn bn dng t bo ung th ngi l
ung th bch cu HL-60, ung th d dy N-87, ung th phi H-460 v ung th gan
HepG2. Kt qu cho thy cc hp cht ny u c hot tnh gy c t bo trn c
bn dng t bo th nghim mc trung bnh (IC50 t 14 M v 22 M) [11].
1.1.3.2. Tc dng vi h tim mch
Mt s alkaloid phn lp c t chi Tetradium c nhiu tc dng tch cc
n h tim mch. Trong mt nghin cu ca Chiou v cng s v tc ng gin c
trn ng mch ch ca ba quinazoline alkaloid phn lp t loi T. ruticarpum
chng minh l rutaecarpine (7), evodiamine (10) v dehydroevodiamine (14) c tc
dng gin mch trn ng mch ch ca chut thc nghim [27].
Nhiu nghin cu trn chut thc nghim chng minh rutaecarpine (7) c
tc dng gin mch [28, 29], ci thin chc nng ca h tim mch v c ch ca
nhp xoang tim nhanh khi s dng khng nguyn gy sc phn v chn thng tim
[30], c ch s co mch gy ra do sc phn v [31], gy gin mch cc on ng
mch mc treo nui cy ca chut th nghim khi s dng tc nhn phenylephrine
gy co mch [32]. Tc dng h huyt p ca rutaecarpine trn chut cao huyt p
theo c ch kch thch s tng hp v phng thch CGRP-l mt cht bo v ni
sinh trong bnh tng huyt p [33, 34]. Tc ng bo v h tim mch do thiu mu
cc b gy ra chn thng c tim ca rutaecarpine l do s kch hot th th
vanilloid phng thch CGRP trn chut thc nghim c mc huyt p bnh
thng [35] hoc huyt p cao t pht [36]. Rutaecarpine cng c tc dng h huyt
19
p v gim ph i ng mch mc treo trong chng tng huyt p thn trn chut
th nghim [37, 51].
Tc dng chng to huyt khi ca rutaecarpine do c ch tp kt tiu cu
gy ra cc nt tc mch [38, 39]. Tc dng chng huyt khi ca rutaecarpine th
hin tng ng vi thuc chng huyt khi aspirin. Khi tim tnh mch,
rutaecarpine ko di ng k thi gian tr s hnh thnh nt tc tiu cu trong cc
tnh mch nh mc treo. Thi gian tr ko di gp khong 1,5 ln so vi nhm i
chng v gp gn hai ln so vi thuc aspirin [40, 41]. Trn m hnh ng vt thc
nghim, rutaecarpine c hiu qu trong vic gim t l t vong do tc mch cp tnh
phi do huyt khi gy ra. Nhng kt qu ny cho thy rutaecarpine (7) c tc
dng chng tp kt tiu cu v c th l mt tc nhn tr liu tim nng cho huyt
khi ng mch [40, 41].
Rang v cng s nghin cu v kt lun v c ch chng sc phn v tim
v chng thiu mu cc b c tim chut lang ca hp cht evodiamine (10) l do
kch thch s phng thch CGRP [42]. Evodiamine (10) cng c nhm nghin
cu ca Chious chng minh l c tc dng gin c khng ph thuc ni mc v
c th nghim nh mt tc nhn c tim nng iu tr ri lon chc nng
cng cng ng vt thc nghim [43]. Trong nghin cu tip theo, nhm nghin
cu ca Chiou cng chng minh tc dng gin mch ca dehydroevodiamine
(14) l do tc ng vo ni mc v phong b th cm th 1-adrenoceptor, kch
hot knh K+ v phong b knh Ca2+ [44].
Trong y hc c truyn, loi T. ruticarpum c s dng rng ri Trung
Quc hng trm nm nay iu tr bnh cao huyt p [45]. T mt phn on dch
chit ca methanol t qu ca loi T. ruticarpum cc nh khoa hc Hn Quc
phn lp c cc quinolone alkaloid l: 39, 41 v 42 l cc tc nhn c tc dng
chn cc th th angiotensin II, v vy cc quinolone alkaloid ny l nhng thnh
phn chnh ca dch chit c tc dng iu chnh huyt p [46].
20
1.1.3.3. Tc dng i vi h thn kinh

Trong cc nghin cu nhm mc ch pht trin cc loi thuc chng thiu
mu no mi t cc sn phm t nhin, Yamahara v cng s c chng minh
dch chit t qu ca loi T. ruticarpum c tc dng tt trong m hnh thiu oximu
no do kali cyanua gy ra chut thc nghim. Phn tch su hn cc thnh phn
hot tnh ch ra rng rutaecarpine (7) v evodiamine (10) l hai hp cht chnh c
tc ng ny [47, 48].
Trong mt nghin cu sng lc v cy thuc, Kim v cc cng s (Hn
Quc) tm ra T. ruticarpum c tc dng bo v h thn kinh v v ngn nga cc
mnh u cacbon ca -amyloid l tin cht protein gy c thn kinh nn c th
hu ch trong vic iu tr cc bnh thoi ha thn kinh v bnh Alzheimer [49].
Nm 1996, Park v cng s ti khoa Dc, i hc Seoul, Hn Quc pht
hin kh nng c ch enzyme acetylcholinesterase v tc dng ci thin tr nh ca
dehydroevodiamine (14) t loi T. rutaecarpa. Tc dng ca dehydroevodiamine
c chng minh mnh hn tacrine l loi thuc iu tr bnh Alzheimer c chp
thun bi FDA [50]. Nhiu cng trnh nghin cu chng minh,
dehydroevodiamine (14) cn c tc dng bo v thn kinh v chng mt tr nh do
c tc ng n s phng thch v hp thu glutamate trn cc t bo no do c
vai tr quan trng trong tr nh v hc tp [51, 52, 53].
Su hp cht quinolone alkaloid, 27, 29, 31, 37, 39 v 42 c phn lp t
loi T. ruticarpum th hin hot tnh c ch enzyme monoamine oxidase B l
mt flavoenzyme c tc dng trong vic iu tr bnh Alzheimer v bnh Parkinson
vi cc gi tr IC50 ln lt l 9,2 M, 55,2 M, 33,2 M, 67,1 M v 15,2 M [9].
1.1.3.4. Tc dng khng vim, gim au
Vim l mt phn ng ca c th nhm bo v c th sng khi cc tc nhn
gy hi cho c th nh: ha hc, vt l, sinh vt, cc yu t c hi ca mi trng,
thiu mu cc b hoc mt tng tc ca cc khng nguyn - khng th [54].
Nm 2009, Liu v nhm nghin cu thuc trng Dc, Trng i hcY,
i hc Quc gia i Loan chng minh c tc dng v c ch khng vim
ca hai hp cht rutaecarpine (7) v evodiamine (10) phn lp t loi T. ruticarpum
21
l do c ch qu trnh tng hp PGE2. Thm vo , c ch khng vin ca

evodiamine cn do c ch c enzyme COX-2, iNOS v yu t NF- B... [55, 56].
Hp cht evodiamine (10) lm gim nng c bn v nng phng thch
angiotensin II ca aldosterone trong t bo glomerulosa thng thn v gim hot
ca enzyme 11 -hydroxylase [57]. Hai hp cht chnh l rutaecarpine (7) v
evodiamine (10) c tc dng kch thch phng thch CGRP [58]. Evodiamine (10)
cng c tc dng c ch s au ca thn kinh cm gic ni tng gy ra bi acetic
acid [59] v c ch knh th th chuyn tip vanilloid loi 1 ln hn khong 3-19
ln so vi capsaicin trn chut thc nghim [60] v c tc dng tng ng vi
capsaicin trn ph qun v tm nh c lp ca chut lang [61].
Rutaecarpine (7) bo v v chng vim lot nim mc d dy gy ra bi
acetylsalicylic acid v stress [62] v bo v nim mc d dy chng li tn thng
do ung ru [63] u c lin quan n s kch thch phng thch CGRP ni sinh
thng qua hot ha th th vanilloid loi 1. Nhiu nghin cu khc cng chng
minh c rng rutaecarpine (7) [64], evodiamine (10) [65] v limonin (72) [64] c
tc dng khng vim gim au trn m hnh ng vt thc nghim.
Thang thuc ni ting c tn Wuzhuyu (Trung Quc) bao gm qu ca loi
T. rutacarpum, gng, nhn sm v to c s dng iu tr chng au na u.
Tc dng cha chng au na u ca n thuc ng y ny l do kch thch
tryptophan hydroxylase 2, mt enzyme kim sot tc sinh tng hp 5-HT trong
no v xc tc cho qu trnh tng hp v gii phng 5-HT trong no [66].
Aurantiamide acetate (15) c tc dng gim au ca chut thc nghim trn
m hnh a nng lm tng thi gian trong qu trnh phn ng kch thch nhit
chut. Hp cht ny cng c ch cc cytokine gy vim, TNF- v Interleukin-2
nn c tc dng gim au khi tim di da m hnh chut b vim khp chn [67].
1.1.3.5. Cc tc dng khc
+ Tc dng dng da
Nm 2012, Jrme Grousson v cng s tm ra dch chit t qu ca loi
T. ruticarpum c tc dng thc y qu trnh tun hon vi mch mu lm cho tng
22
sng ca da. Nghin cu chng minh dch chit t tri cy. T. ruticarpum lm
gin mch mu do kch thch vi tun hon da bng cch iu chnh nng phng
thch nitric oxide ngoi bo trn da ca cc tnh nguyn vin [68].
Dch chit ca loi T. ruticarpum c tc dng chng tia cc tm B trn da
[69]. Hn hp gm rutaecarpine (7), evodiamine (10) v dehydroevodiamine (14)
c chng minh c tc dng ngn tia cc tm gy ra s phng thch PGE2 t
cc t bo sng v ban trn da ngi [70]. Rutaecarpine (7) c ch tia cc tm A
gy ra cc loi phn ng oxi ha v ngn chn UVA trn t bo sng HaCaT ca
ngi [71].
Rutaecarpine v evodiamine cng c tc dng iu tr vim da d ng v
vim mi do c ch globulin min dch E trn chut th nghim [72].
+ Tc dng iu nhit c th
Trong s cc hp cht alkaloid chnh c phn lp t qu ca loi T.
ruticarpum, hp cht evodiamine (10) ngn chn tc dng h nhit c th chut
thc nghim do hp cht gy st ngoi sinh chlorpromazine gy ra [73].
Khi tim dehydroevodiamine (14) hoc evodiamine (10) vo mng bng
chut th nghim, cc hp cht ny lm gim nhit c th chut. Thm vo
, c hai hp cht 10 v 14 c tc dng gim st khi tim vng di i ca
chut thc nghim, gy st bi chlorpromazine [74].
+ Tc dng chng bo ph
Nhiu nghin cu chng minh tc dng chng bo ph ca evodiamine
(10) v rutaecarpine (7). Evodiamine c cc tc dng chng to m [75, 76, 77].
Shi v cng s tm ra c ch tc dng l do gim hot ca
neuropeptide Y v tng mc lu hnh ca leptin [78, 79], tng t nh capsaicin
do tc ng n UCP-1 l mt protein trong ty th ca cc m m nu, c tc dng
t chy nng lng (tc l t m trng), dn n gim trng lng hay gim
lng m trong c th [80, 81].
+ Tc dng chng bnh tiu ng
Bak v cng s nghin cu hot tnh khng tiu ng ca evodiamine
(10); evodiamine phi hp vi thuc rosiglitazone; mt loi thuc tr bnh tiu
ng nhng tc dng ph nh tng nguy c nhi mu c tim, to m trong c th,
23
tng cn v nhim c gan. Khi s dng phi hp, evodiamine gim cc tc dng
ph ca rosiglitazone m khng lm nh hng ti tc dng chnh ca thuc. Tuy
nhin, hp cht 10 cng c tc dng gim lng ng v nng insulin huyt
tng v c tc dng ci thin sc khng insulin tng ng vi thuc
rosiglitazone [82]. Hydroxyevodiamine (12) c phn lp t T. ruticarpum c kh
nng c ch hot tnh enzyme aldose reductase [83].
Hp cht skimmin (89) cng c chng minh gim ng k hm lng ure
mu, lm tng bi tit albumin niu v creatinine huyt thanh trn chut. iu tr
bng skimmin (89) c th ci thin ng k chc nng thn v ngn chn s lng
ng IgG cng nh s pht trin ca tn thng thn trn chut thc nghim vim
cu thn mng [84, 85].
Umbelliferone (92) v glibenclamid lm gim hm lng insulin v ng
huyt trn chut thc nghim mc bnh tiu ng. Ngoi ra, umbelliferone (92) c
tc dng bo v thnh phn mng t bo acid bo ca gan v thn v c tc dng h
tr chng oxi ha v chng tng lipid huyt [86].
+ Tc dng khng vi sinh vt
Trong nghin cu sng lc 300 mu chit xut t tho dc, Zheng v cng
s pht hin dch chit ca loi T. ruticarpum c xp loi th tm trn mi
mu th hin hiu qu tc dng c ch khng nguyn b mt vim gan B [87].
Ngoi ra, cc hp cht quinolone alkaloid 10, 29, 31, 33, 41 v 42 phn lp t loi
T. ruticarpum c pht hin c kh nng c ch qu trnh h hp v tiu dit vi
khun Helicobacter pylori gy bnh d dy [88, 89, 90]. Cng t dch chit ca loi
ny, Thuille v cng s tm thy kh nng dit t cu khun gram dng,
Pseudomonas aeruginosa v Candida albicans [91].
Nm hp cht quinolone alkaloid: 29, 37, 39, 41, 42 t loi T. ruticarpum c
hot tnh khng lao, trn c ba chng lao th nghim l: Mycobacterium fortuitum,
Mycobacterium smegmatis v Mycobacterium phlei. Hp cht evocarpine (39) c
hot tnh mnh nht vi gi tr MIC l 2 g/mL trn c ba chng lao. Trn chng
lao M. fortuitum, hot tnh ca evocarpine mnh gp tm ln so vi ethambutol v
24
tng ng vi isoniazid. Trn chng lao M. smegmatis, hp cht 39 c hot tnh

ln gp hai ln so vi isoniazid, nhng tc dng km ethambutol hai ln [92, 93].
+ Tc dng i vi h tiu ha
Dch chit ca T. ruticarpum c tc dng c ch s co tht ng rut v
iu tr bnh tiu chy gy ra do du thu du trn chut thc nghim [94] v bo
v cc tn thng trong d dy chut do ethanol gy ra [95, 96].
Evodiamine (10) c ch qu trnh co bp tht trong h tiu ha chut thc
nghim theo c ch lin quan n s phng thch cholecystokinin v kch hot th
th cholecystokinin 1 [97]. Tc dng chng nn ca dch chit ethanol ca thang
thuc Wuzhuyu l do c ch 5-HT v th th histamin [98].
Khi iu tr bng skimmianine (20) lm gim s cn au trn chuc thc
nghim b gy au qun bng acetic acid so vi nhm i chng. Ngoi ra,
skimmianine (20) l tc nhn c ch s vn chuyn thc n trong h tiu ha [99].
+ Chng d ng
Umbelliferone (92) c pht hin lm gim ng k bch cu i toan
trong dch ra ph qun v lm gim lng cht nhy tit ra t chut thc nghim
b vim phi [100].
+ Hot tnh khng HIV
Alkaloid, decarine (1) th hin hot tnh khng HIV trn cc t bo H9
(IC50: 22,6 g/mL, EC50 <0,1 g/mL). Nghin cu v mi lin gia cu trc-hot
tnh ch ra nhm th 8-OH ca decarine c vai tr quan trng trong vic xut
hin hot tnh khng HIV.
Ngoi ra mt s hp cht khc nh skimmianine (20) v isopimpinellin (59)
cng c hot tnh ny vi gi tr EC50 ln lt l 7,41 v 0,67 g/mL [101].
+ Tc dng chng say ru
Dch chit t qu ca loi T. ruticarpum c tc dng gim nng cn trong
mu do tc dng n cc enzyme alcohol dehydrogenase (ADH), aldehyde
dehydrogenase (ALDH), CuZn superoxide dismutase (CuZn SOD), glutathione
peroxidase type 5 (GPX5) v catalase (CAT). Tc dng chng say ru ca T.
25
ruticarpum c tc dng tng t thuc chng say khc c thng mi trn th

trng [102].
+ Tc dng co t cung
King v cng s th nghim v chng minh c hai alkaloid phn lp t
dch chit ca qu ca loi T. ruticarpum l: rutaecarpine (7) v dehydroevodiamine
(14) c tc dng gy co t cung in vitro trn t cung chut c lp. S c mt ca
rutaecarpine (7) trong qu ca T. ruticarpum l thnh phn quan trng trong cc n
thuc y hc c truyn Trung Quc iu tr ri lon sinh sn n [103, 104].
+ Tc dng chng cn trng
Mt s limonoid v cc dn xut ca limonin nh limonin (72) v limonin
diosphenol (62) c tc dng kim sot cn trng b cnh cng Colorado
(Leptinotarsa decemlineata) trn khoai ty v u trng Spodoptera frugiperda
[105]. Ngoi tc dng kim sot cn trng gy hi, cc limonoid cng c s dng
trong kim sot u trng ca mui rt hiu qu, in hnh nh hp cht
calodendrolide (56) [106].
Trong by furanocoumarin t tri cy sy kh ca loi T.daniellii c bn
hp cht l: 94, 95, 96 v 99 th hin hot tnh dit hai loi u trng bm m
Spodoptera littoralis v Heliothis virescens [7].
Kt lun:
Cc hp cht phn lp c t chi Tetradium th hin nhiu hot tnh a
dng v hu ch nh: hot tnh khng ung th (phi, i trng, vm hng v da v
cc t bo ung th v v ung th d dy...), tc dng i vi h tim mch, h thn
kinh, tc dng khng vim gim au, dng da, tr bnh tiu ng, khng HIV,
gim bo v tc dng iu nhit ... Tuy nhin, phn ln cc hp cht th hin cc
hot tnh v tc dng ny trong cc loi ca chi Tetradium phn ln u thuc lp
cht alkaloid nh: decarine (1),
rutaecarpine (7), evodiamine (10), dehydro-
evodiamine (15) v mt s hp cht quinolone alkaloid...; hoc lp cht limonoid

nh: limonin (68), skimmin (84), umbelliferone (87)...
26
1.2. GII THIU V CY DU DU L NHN

1.2.1. c im thc vt
Tn khoa hc:
Tetradium glabrifolium (Benth.) Hartl.).
Tn ng ngha:
Ampacus meliaefolia (Hance ex Walp.) Kuntze; Boymia
glabrifolia Champion ex Bentham; Evodia ailanthifolia Pierre; Evodia fargesii

Dode; Evodia glabrifolia (Champ. ex Benth.) C. C. Huang; Evodia glauca Miq.;
Evodia meliaefolia (Hance ex Walp.) Benth.; Evodia poilanei Guillaumin; Evodia
yunnanensis C. C. Huang; Euodia taiwanensis T. Yamaz.; Megabotrya meliaefolia
Hance ex Walp.; Tetradium glabrifolium var. glaucum (Miq.) T.;
Tn Vit Nam:
Du du l nhn
Chi:
Tetradium
H:
Cam qut (Rutaceae)
c im m t:
L cy i mc, c th cao n 20 mt, v t nt, cnh
non c lng. Cnh l di 14-38 cm c t 5-19 l ph. L bn rng, hnh trng hoc
hnh li mc, y bt i xng, ba nguyn, khng lng, gn ph, kch thc l
1,7-6 4-15cm, cung ph 3-5mm; cung c lng. Hoa n thnh chm, kch thc
t 9-19cm. Mi bng hoa c bn hoc 5 cnh, dy khong 0,5 mm. Cnh hoa mu
xanh l cy, vng hoc trng, khi kh chuyn sang mu trng c n mu nu. Qu
c ba nang, cha lp tht xp bao bn ngoi mt lp v mng khi chn c mu en
bng, trong qu mi nang c 1 ht trn, mu en, kch thc t 2,5 4 mm. Hoa n
t thng 6 n thng 9. Qu xut hin t thng 9 n thng 12 [107].
Phn b: Vng ng (Nht Bn, Trung Quc, ng bc n , Vit Nam,
Philippin, Innxia, Malaysia, Myanma v Thi Lan, Lo, Campuchia) [107].
1.2.2. Cng dng cha bnh
Trong y hc c truyn, cy du du l nhn c s dng nhiu lm thuc tr
tn thng do ng, gy xng, thp khp. Thn v l cy dng tr vim thn, ph
thng, dng ngoi cha chn thng, nga, eczema. L cy cn c dng nu
nc tm cho b hoc nu nc c ra vt thng, tm gh l v gi chng
vi gim hay lm nng p sng v. Qu v v c dng sc ung li tiu hoc
i tiu tin, cha kit l, to bn v thp khp [108].
27
Trung Quc, l cy du du l nhn cn c dng cha tr cc bnh l

lot t chi mn tnh v bnh au d dy [109].
1.2.3 Tnh hnh nghin cu trn th gii
Nghin cu ha hc u tin v cy du du l nhn c cng b nm 1987
do nhm nghin cu ca Kwok ti khoa Dc trng i hc Strathclyde, Scotland.
Cng trnh cng b cu trc su hp cht t thn, v v r cy du du l nhn,
l cc hp cht: 1-hydroxyrutaecarpine (8), arnottianamide (16), isolimonexic
acid (64), rutaevine (67), limonin (72) v rutaevinexic acid (77) [110].
Nm 1995, nhm ca Wu (H Quc gia Cheng Kung, i Loan) nghin cu
thnh phn ha hc ca l cy du du l nhn v phn lp c 29 hp cht, bao gm:
ba alkaloid, rutaecarpine (7), methyl--carboline-1-carboxylate (21), strychnocarpine
(22); nm triterpenoid, squalene (54), -amyrin acetate (57), taraxerone (59), epitaraxerol (60) v taraxerol (61); nm flavonoid, liquiritin (80), kaempferol-3-O-D-xylopyranoside (81), nicotitlorin (84), rutin (85) v juglanin (86); nm coumarin,
skimmin (89), isofraxoside (90), fraxin (91), umbelliferone (92) v scopoletin (93);
by benzenoid l: p-hydroxy benzaldehyde (101), p-hydroxybenzoic acid (102),
protocatechuic acid (103), gallic acid (110), methylgallate (111), -glucogallin
(114) v methylchlorogenate (120); hai tannin, corilagen (131) v ellagic acid (132);
mt saccaride, myo-inositol (133) v mt nucleoside, adenoside (135) [111].
Cng trong nm 1995, nhm ca Wu tip tc cng b cu trc ca bn su
hp cht c phn lp t li thn cy du du l nhn, trong c 3 hp cht mi l
evomeliaefolin (53), evofolin A (115), evofolin B (116) v 43 hp cht bit gm:
decarine
(1),
norchelerythrine
(2),
bocconoline
(3),
6-acetoneyl-5,6-
dihydrochelerythrine (4), oxychelerythrine (5), rutaecarpine (7), hortiacine (9),

arnottianamide (16), dictamnine (17), robustine (18), -fagarine (19), skimmianine
(20), 4-methoxy-1-methyl-2-quinolone (52), atractylenolide III (55), lupeol (58), 12hydroxyevodol (65), evodol (66), rutaevine (67), graucin A (69), 6-acetoxy-5epilimonin (71), limonin (72), umbelliferone (92), p-hydroxy-benzaldehyde (101), phydroxybenzoic
acid
(102),
methylparaben
28
(104),
methylsyringate
(105),
syringaldehyde
(106),
vanillin
(107),
3,4,5-trimethoxybenzylalcohol
methylvanillate
(109),
methyl-p-hydroxycinnamate
(112),
(108),
trans-4'-hydroxy-3'-
methoxycinnamaldehyde (113), evofolin C (114), -hydroxypropioguaiacone (117),

2'-hydroxy-4'-methoxyacetophenone (118), -sitosterol (121), sitosterylglucoside
(122),
hortiamide
(126),
cis-N-p-coumaroyltyramine
(127),
trans-N-
coumaroyltyramine (128), cis-N-feruloyltyramine (129) trans-N-feruloyltyramine

(130) v (-)-matariesinol (134) [109].
1.2.4. Tnh hnh nghin cu Vit Nam
Trong ti liu cy thuc v ng vt lm thuc Vit Nam, Huy Bch v
cc cng s cy du du l nhn Vit Nam c s dng nh mt v thuc nam
c rt nhiu cng dng cha bnh [108].
Kt lun:
Mc d cy du du l nhn c s dng trong y hc c truyn, nhng
hin nay Vit Nam cha c nghin cu no v loi ny. Vic nghin cu thnh
phn ha hc v cc hot tnh sinh hc s gp phn lm sng t thm thnh phn
ha hc cng nh cc kinh nghim s dng cy thuc ny trong dn gian v c th
loi ti Vit Nam nh hng cho nhng nghin cu ng dng tip theo.
29
CHNG 2
I TNG V PHNG PHP NGHIN CU
2.1. MU THC VT
Mu v thn v mu l ca cy du du l nhn c thu hi vo thng 6 nm
2011 ti Ty Thin, Tam o, Vnh Phc. Tn khoa hc c TS. Nguyn Th
Cng, Vin Sinh thi v Ti nguyn sinh vt gim nh. Mu tiu bn c lu tr
ti Vin Ha sinh bin v Vin Sinh thi v Ti nguyn sinh vt, Vin Hn lm
Khoa hc v Cng ngh Vit Nam.
Mu l cy du du l nhn
Mu tiu bn thc vt kh
Hnh 1. Mu thc vt v mu tiu bn kh ca cy du du l nhn.

2.2. PHNG PHP PHN LP CC HP CHT
2.2.1. Sc k lp mng (TLC)
Sc k lp mng c thc hin trn bn mng trng sn DC-Alufolien 60
F254 (Merck 1,05715), RP18 F254 (Merck). Pht hin cht bng n t ngoi hai
bc sng 254 nm v 365 nm hoc dng thuc th l dung dch sulforic acid 10%
c phun u ln bn mng, sy kh ri h nng t t n khi hin mu.
30
2.2.2. Sc k lp mng iu ch
Sc k lp mng iu ch thc hin trn bn mng trng sn silica gel 60G
F254 (105875, Merck), pht hin vt cht bng n t ngoi hai bc sng 254 nm
v 365 nm, hoc ct ra bn mng phun thuc th l dung dch sulforic acid 10%,
h nng pht hin vt cht, ghp li bn mng nh c xc nh vng cht, sau
co lp silica gel c cht, gii hp ph v tinh ch li bng cch kt tinh trong
dung mi thch hp.
2.2.3. Sc k ct (CC)
Sc k ct c tin hnh vi cht hp ph l silica gel pha thng vi kch
thc ht 0,040-0,063 mm (240-430 mesh); pha o s dng loi YMC c c ht l
30-50 m (Fujisilica Chemical Ltd.); nha trao i ion s dng loi Diaion HP-20
(Misubishi Chemical Indutries Co., Ltd.).
2.3. PHNG PHP XC NH CU TRC HA HC
xc nh cu trc ha hc ca cc hp cht s dng kt hp xc nh cc
thng s vt l bng cc phng php ph hin i [112, 113] ng thi kt hp
phn tch, tra cu ti liu tham kho. Cc thit b v phng php s dng gm:
2.3.1. im nng chy (Mp)
im nng chy c o trn my Kofler micro-hotstage ca Vin Ha sinh
bin - Vin Hn lm Khoa hc v Cng ngh Vit Nam.
2.3.2. quay cc ([]D)
quay cc c o trn my JASCO DIP-1000 KUY polarimeter ca Vin
Ha sinh bin - Vin Hn lm Khoa hc v Cng ngh Vit Nam.
2.3.3. Ph khi lng (MS)
Ph khi lng phun m in t ESI-MS c o trn my Agilent 1200
TRAP, Vin Ha hc cc hp cht thin nhin.
Ph khi lng phn gii cao HR-ESI-MS o trn my FT-ICR-Mass
spectrophotometer ti Vin Ha hc.
31
2.3.4. Ph cng hng t nhn (NMR)

Ph NMR o trn my Bruckker avance 500 MHz (Cht chun ni l TMS),
ti Vin Ho hc, Vin Hn lm Khoa hc v Cng ngh Vit Nam.
Cc k thut ph cng hng t ht nhn c s dng bao gm:
Ph cng hng t ht nhn mt chiu: 1H-NMR, 13C-NMR v DEPT.
Ph cng hng t ht nhn hai chiu: HSQC, HMBC.

Dung mi c s dng bao gm cc dung mi DMSO-d6, CD3OD, CDCl3.
Vic la chn dung mi o ph thuc vo bn cht ca tng mu, theo nguyn tc

dung mi phi ha tan hon ton mu th.
2.4. PHNG PHP XC NH HOT TNH SINH HC
2.4.1. Hot tnh gy c t bo in vitro
Cc hp cht phn lp t cy du du l nhn c th hot tnh gy c t
bo in vitro trn 6 dng tn bo ung th, c th nghim ti Phng Th nghim sinh
hc, Vin Cng ngh sinh hc, Vin Hn lm Khoa hc v Cng ngh Vit Nam.
Nguyn liu
Nguyn liu:
Cc dng t bo: KB (Human epidemoid carcinoma - ung th biu m), Fl
(Fibril sarcoma of uteus - Ung th mng t cung), RD (Rhabdo sarcoma -Ung th
mng tim), LU (Human Lung carcinoma - Ung th phi ngi), SW480 (Human
colon adenocarcinoma cell line - Ung th tuyn i trng ngi), LNCaP (Human
prostatic carcinoma -ung th tin lit tuyn ngi).
Mi trng nui cy t bo: DMEM (Dulbeccos modified eagle medium)
c b sung L-glutamine, sodium piruvat, sodium bicacbonat; fetal bovine serum;
Ha cht khc: DMSO, trichloroacetic acid, phosphate buffered saline,
sulforhodamine B, acetic acid, tris base, trypsin.
Cht i chng dng tnh: Ellipticine.
Thit b: T m CO2, t lnh su - 840C, t lnh thng, my li tm, my c
Elisa; Box Laminar PII, bnh nit lng, cn phn tch, my o pH, bung m t
32
bo, knh hin vi soi ngc, bnh nui cy t bo, cc typ dng 1 ln (phin vi lng
96 ging, pipet pasteur, cc u tip cho micropipet)
Phng php
Phng php nui cy t bo in vitro
Cc dng t bo ung th c nui cy di dng n lp trong mi trng
nui cy DMEM (Dulbeccos modified eagle medium) cng vi 2 mM Lglutamine, 1,0 mM sodium pyruvate v fetal bovine serum 10%.
T bo c cy chuyn sau 3-5 ngy vi t l 1:3 v nui trong t m CO2
iu kin 37oC, 5% CO2.
Php th sinh hc xc nh tnh c t bo (cytotoxic assay)
Nguyn l ca phng php
Phng php th c t bo in vitro c Vin Ung th Quc gia Hoa K
(National Cancer Institute - NCI) xc nhn l php th c t bo chun nhm
sng lc, pht hin cc cht c kh nng km hm s pht trin hoc dit t bo ung
th iu kin in vitro. Php th ny c thc hin theo phng php ca Monks
(1991) [114] nhm xc nh hm lng protein t bo tng s da vo mt
quang hc (OD) o c khi thnh phn protein ca t bo c nhum bng
sulforhodamine B. Gi tr OD t l thun vi lng sulforhodamine B gn vi phn
t protein, do lng t bo cng nhiu th gi tr OD cng ln.
Php th c thc hin trong iu kin c th nh sau:
Cht th c pha trong DMSO 10%, sau a vo cc ging ca khay 96
ging c di nng 0,8; 4; 20 v 100 g/mL. Trypsin ha t bo th nghim
lm ri t bo v m trong bung m iu chnh mt cho ph hp vi th
nghim. Thm vo cc ging th nghim lng t bo ph hp trong 180 l mi
trng v pht trin trong vng t 3-5 ngy. Mt khay 96 ging khc khng c
cht th nhng c t bo ung th (180L) s c s dng lm i chng ngy 0.
Sau 1 gi, a i chng ngy 0 s c c nh t bo bng trichloracetic acid.
Sau giai on pht trin trong t m CO2, t bo c c nh vo y ging
bng trichloracetic acid trong 30 pht, c nhum bng sulforhodamine B trong 1
33
gi 37 oC. b sulforhodamine B v cc ging th nghim c ra 3 ln bng

5% acetic acid ri kh trong khng kh nhit phng. Cui cng, s dng 10
mM tris base ha tan lng sulforhodamine B bm v nhum cc phn t
protein, a ln my lc a lc nh trong 10 pht v s dng my ELISA (BioRad) c kt qu v hm lng mu ca cht nhum sulforhodamine B qua ph
hp ph bc sng 515 nm. Kh nng sng st ca t bo khi c mt cht th s
c xc nh thng qua cng thc sau:
[OD (cht th) OD (ngy 0)] 100
% sng st =
% c ch
OD (i chng m) OD (ngy 0)
100% - % sng st
Cc php th c lp li 3 ln m bo tnh chnh xc. Ellipticine

(Sigma) c s dng nh l cht i chng dng v c th nghim cc nng
0,08, 0,4, 2, 10 g/mL. DMSO 10% c s dng nh i chng m.
2.4.2. Phng php nh gi hot tnh khng lao
Hot tnh khng lao c th nghim ti Phng Hp cht t nhin, i hc
Osaka, Nht bn.
Cc hp cht c phn lp t cy du du l nhn c th hot tnh khng
lao trn chng vi khun Mycobacterium bovis (BCG) v Mycobacterium smegmatis
bng phng php MABA (microplate alamar blue assay: php th vi lng s
dng thuc nhum xanh Alamar) [115].
Nguyn tc ca phng php:
Da vo qu trnh pht trin ca vi khun Lao lm din ra qu trnh oxi ha
kh lm thuc th Alamar blue pht hunh quang. o bc sng kch thch 530
nm v bc sng pht x 590 nm. c kt qu sau 7 ngy.
Gi tr MIC ca cht th hot tnh c xc nh l nng thp nht khng
gy pht hunh quang tng
Phng php tin hnh:
Chng vi khun lao c pht trin trong mi trng Middlebrook 7H9
c b xung thm 0,2% glycerol (v/v), 0,05% tween-80 v dch nui 10% (v/v)
34
(gm: oleic acid, albumin, dextrose, catalase). Mi trng nui cy ny c ly tm

vi tc 3150 vng/pht trong 15 pht 4oC c ra li 2 ln, ha li trong m
phosphat saline. Dch t bo c lc qua mng lc, kch thc 8 m, sau c
lu gi -80oC.
Mu th c ha tan trong DMSO nng 10 mg/mL, sau pha long
thnh dy cc nng dng cho th nghim t 2 -128 M. Mu th c pha long
2 ln trong mi trng Middlebrook 7H12, sau a 100 l mu vo cc ging
trong a 96 ging sau thm 100 l dch c cha chng vi khun lao. a c
trong 7 ngy 370C vi p sut thng. Ngy th 7 thm 12,5 l tween-80 20%
v 20 l thuc th Alamar blue vo mi ging. tip 370C trong 16-24 gi.
Mc hunh quang ca mi ging c c bc sng kch thch 530
nm v bc sng pht x 590 nm.
Gi tr MIC c xc nh l nng thp nht khng gy pht hunh quang
tng quan n 90% so vi ging iu khin khng c vi sinh vt.
2.4.3. Phng php nh gi hot tnh chng oxi ha
Hot tnh chng oxi ha c th nghim ti: Phng Th nghim sinh hc,
Vin Cng ngh sinh hc, Vin Hn lm Khoa hc v Cng ngh Vit Nam theo
phng php dit gc t do DPPH.
Nguyn tc ca phng php:
1,1-diphenyl-2-picrylhydrazyl (DPPH) c kh nng to ra cc gc t do bn
trong dung dch ethanol bo ho. Khi cho cc cht th nghim vo hn hp ny, nu
cht c kh nng lm trung ho hoc bao vy cc gc t do s lm gim cng hp
ph nh sng ca cc gc t do DPPH. Hot tnh chng oxi ho c nh gi thng
qua gi tr hp ph nh sng ca dch th nghim so vi i chng khi c trn my
Elisa bc sng 515 nm [116].
Phng php tin hnh:
Phng php sng lc s b kh nng by gc t do trn phin 96 ging.
Tin hnh nh sau:
Chun b mu th nghim:
To dung dch c cc gc t do: DPPH c pha 300 M trong ethanol.
35
Mu i chng dng tnh 5 mM acscorbic acid

Tin hnh th nghim:
Trn mu v DPPH trn phin 96 ging.
Dy th nghim: 10 l mu +190 l DPPH trong ethanol.
Dy i chng m tnh: 10 l DMSO 10% +190 l DPPH trong ethanol.
Dy mu trng (Blank): 10 l mu +190 l ethanol.
Dy i chng dng tnh: 10 l mu +190 l DPPH trong ethanol.
Phin c bc kn trnh nh sng v trong t m 37oC trong 2 gi. c
kt qu trn my Elisa bc sng 515 nm
* Tnh kt qu
- Tnh gi tr kh nng by cc gc t do - SC%: Gi tr trung bnh ca SC%
c a vo chng trnh Microsoft Office Excel x l s liu tm ra % trung
bnh lch chun ca php th c lp li 3 ln theo cng thc:
OD th nghim - OD mu trng
SC% = [100 -
100]
OD chng m tnh
lch tiu chun tnh theo cng thc ca Ducan nh sau:
(xi - x )2
n-1
Gi tr hot ng SC% >50% mu c coi l c biu hin hot tnh s c
chn ra tm gi tr IC50.
Tm gi tr c ch EC50
Pha mu theo 5 thang nng , gi tr IC50 c a vo chng trnh
Table Curve, thng qua nng cht th v % hot ng ca cht th tnh ra nng
ca cht th nghim m 50% cc gc t do c to bi DPPH c trung
ho bi cht th theo cng thc:
1
= a + b.ln X
Y
Trong :
Y: Nng cht th;
36
X: Gi tr SC (%).
2.4.4. Hot tnh khng vi sinh vt kim nh

Hot tnh khng vi sinh vt kim nh ca cc hp cht phn lp c t cy
du du l nhn, c tin hnh theo phng php ca Vander Bergher v Vlietlinck
[117] trn cc phin vi lng 96 ging, ti Phng Th nghim sinh hc, Vin Cng
ngh sinh hc, Vin Hn lm Khoa hc v Cng ngh Vit Nam.
* Nguyn liu:
Mu th c chun b theo mt quy trnh c xy dng thng nht ti
Vin Cng ngh sinh hc.
Cc chng vi sinh vt kim nh bao gm:
Vi khun Gr (+): Staphylococcus aureus; Bacillus subtillis; Lactobacillus
fermentum.
Vi khun Gr (-):Salmonella enterica; Escherichia coli; Pseudomonas
aeruginosa.
Nm mc: Aspergillus niger; Fusarium oxysporum.
Nm men: Candida albicans; Saccharomyces cerevisiae.
Khng sinh kim nh: Ampicilin i vi vi khun Gr (+); tetracylin i vi
vi khun Gr (-); nystatin i vi nm si v nm men.
Cch pha khng sinh:
Khng sinh pha trong DMSO vi nng : ampixilin: 50mM, tetracylin:
10mM, nystatin: 0,04mM
Mi trng nui cy vi sinh vt:
Mi trng duy tr v bo tn ging: Saboraud Dextrose Broth i vi nm
men v nm mc; Trypcase Soya Broth i vi vi khun.
Mi trng th nghim: Eugon broth i vi vi khun v Myco phil i vi
nm.
Phng php tin hnh:
- Hot tnh khng vi sinh vt kim nh nh gi hot tnh khng sinh ca
cc mu chit c tin hnh trn cc phin vi lng 96 ging (96-well microtiter
plate) theo phng php ca Vander Bergher v Vlietlinck (1991) [117], ang c
p dng ti trng i hc Dc, i hc Tng hp Illinois, Chicago, M.
37
Bc1: Sng lc s b tm cht c hot tnh

Chun b vi sinh vt:
Nm c duy tr trong mi trng dinh dng nu phn nguyn liu
v phng php. Cc chng kim nh c hot ho trc khi tin hnh th
nghim trong mi trng dinh dng dch th c bit (24 gi i vi vi khun, 48
gi i vi nm). Sau c pha long ti nng 0,5 n v Mc Fland.
Chun b mu th:
- Ho tan cc chit phm trong dung dch DMSO bng my Vortex vi nng
4-10 mg/ml.
- T dung dch gc nh sang phin vi lng 96 ging, mi ging 10 l mu.
- Nh vo mi ging c mu sn 190 l vi sinh vt hot ho.
i chng dng: Khng sinh + vi sinh vt kim nh.
i chng m: ch c vi sinh vt kim nh.
- trong t m 37oC/24 gi i vi vi khun v 300C/48 gi i vi nm.
- c kt qu:
Mu dng tnh khi nhn bng mt thng thy trong sut, khng c vi sinh
vt pht trin, ging nh hnh nh cc ging chng m tnh. Mu dng tnh
bc 1 s c tip tc th bc 2 tnh gi tr nng c ch ti thiu (MIC).
Bc 2: Tm nng c ch ti thiu (MIC) ca cc hp cht c hot tnh:
Cc bc tin hnh nh bc 1: cc mu dng tnh bc 1 c pha
long theo cc thang nng thp dn, t (5-10) thang nng tnh gi tr c
ch ti thiu m vi sinh vt b c ch pht trin gn nh hon ton.
38
CHNG 3
THC NGHIM V KT QU
3.1. PHN LP CC HP CHT T CY DU DU L NHN
3.1.1. Phn lp cc hp cht t mu l ca cy du du l nhn
Mu l cy du du l nhn c phi kh, nghin thnh bt (3,5 kg), sau
chit trong methanol (35 lt) bng thit b chit siu m (50oC, 3 h). Dch chit
c lc qua giy lc, gom li v ct loi dung mi p sut gim thu c 210,0 g
cn chit methanol. Cn chit ny c ha tan vo 3 lt nc ct v tin hnh chit
phn b ln lt vi n-hexane v ethyl acetate (mi loi 3 3 lt). Cc dch chit nhexane, ethyl acetate c ct thu hi dung mi thu c cc cn dch tng ng nhexan (L-H, 62,0 g) v (L-E, 78,0 g) v lp nc (L-N, 70,0 g).
Cn chit ethyl acetate (78,0 g) c ha tan vi mt lng ti thiu ethyl
acetat sau tm vi 90,0 g silica gel. Tin hnh phn tch bng ct nhi silica gel
pha thng, sau ra gii bng chloroform/methanol (25/1 1/1) thu c su
phn on chnh L-E1 (15,0 g), L-E2 (11,0 g), L-E3 (5,0 g), L-E4 (4,5 g), L-E5 (5,0
g), L-E6 (7,0 g).
L-E3 (5,0 g) c phn tch bng bng sc k ct silica gel pha thng, ra
gii bng hn hp chloroform/acetone/ nc (1/3/0,1), thu c ba phn on LE3A (0,8 g), L-E3B (1,2 g) v L-E3C (0,9 g). L-E3B tip tc phn tch bng sc k
ct silica gel pha thng s dng h dung mi chloroform/methanol (3/1), thu c
hp cht TG14 (20 mg).
L-E4 (4,5 g) c phn tch bng bng ct silica gel pha thng, ra gii
bng hn hp chloroform/acetone/nc (1/3/0,1), thu c ba phn on L-E4A
(1,0 g), L-E4B (1,1 g), L-E4C (0,8 g). L-E4B c phn tch bng sc k ct silica
gel pha thng s dng h dung mi ra gii chloroform/methanol (3/1), thu c
hp cht TG22 (7 mg).
L-E5 phn tch bng sc k ct silica gel pha thng vi h dung mi ra
gii chloroform/ethyl acetate (3/1), thu c hp cht TG8 (10 mg).
39
Hnh 2. S phn lp cc hp cht t mu l cy du du l nhn.

40
Lp nc (L-N, 70,0 g) cho qua ct sc k trao i ion vi cht hp ph l

Diaion HP-20 vi h dung mi tng dn nng methanol trong nc (0, 25, 50, 75
v 100 %) thu c nm phn on L-N1 (8,0 g), L-N2 (8,2 g), L-N3 (10,0 g), LN4 (15,0 g) v L-N5 (7,0g).
L-N3 c phn tch bi sc k ct silica gel pha thng, ra gii gradien
bng h dung mi chloroform/methanol (20/1 1/1) thu c nm phn on LN3A (2,3 g), L-N3B (2,1 g), L-N3C (2,0 g), L-N3D (1,9 g) v L-N3E (2,0 g). Tip
tc phn tch L-N3C (2,0 g) bng sc k ct silica gel pha thng v h dung mi
chloroform/methanol (3/1), thu c ba phn on L-N3C1 (0,8 g), L-N3C2 (0,8 g)
v L-N3C3 (0,8 g). Ba phn on ny ln lt chy sc k ct silica gel pha o
bng h dung mi methanol/ nc (1/1), thu c cc hp cht TG1 (10 mg),
TG21 (20 mg) v TG23 (20 mg).
L-N4 (15,0 g) c ha tan trong mt lng ti thiu dung mi methanol sau
tm vi 30,0 g silica gel, c quay di p sut thp thu c bt mu. Bt ny
c phn tch bng sc k ct silica gel pha thng ra gii bng h dung mi
chloroform/methanol (20/1 1/1) thu c nm phn on L-N4A (2,0 g), L-N4B
(3,2 g), L-N4C (2,0 g), L-N4D (2,5 g), L-N4E (3,0 g). L-N4C c phn tch bng
sc k ct silica gel pha thng ra gii bng h dung mi chloroform/methanol
(3/1) thu c cc hp cht TG13 (30 mg), TG15 (10 mg). Cc hp cht TG11 (8
mg) v TG12 (60 mg) c tinh ch t L-N4D (2,5 g) bng cch s dng sc k ct
silica gel pha thng vi h dung mi ra gii chloroform/methanol/nc (4/1/0,1).
Hp cht TG16 (20 mg) c tinh ch t L-N5 (7,0 g) bng ct sc k silica gel
pha thng, s dng h dung mi chloroform/methanol (45/1).
3.1.2. Phn lp cc hp cht t mu v thn ca cy du du l nhn
V cy du du l nhn c phi kh, nghin nh thu c 2,4 kg bt. Bt
ny c ngm chit trong methanol (3 lt 3 ln) v s dng thit b chit siu m
(50oC, 3 h). Cc phn dch chit c gom li lc qua giy lc v ct thu hi dung
mi thu c 287,0 g cn chit methanol. Cn chit c ha tan vo 3 lt nc ct
v tin hnh chit phn b ln lt vi n-hexane, ethyl acetate (3 3 lt). Cc dch
41
chit n-hexane, ethyl acetate c ct thu hi dung mi thu c cc cn dch tng

ng n-hexane (V-H, 91,0 g), ethyl acetate (V-E, 132,0 g) v lp nc (V-N).
Cn chit ethyl acetate (52,0 g) c ha tan vi mt lng ti thiu ethyl
acetate sau c tm vo 200,0 g silica gel. Tin hnh phn tch bng ct silica
gel pha thng v ra gii vi gradient h dung mi n-hexane/acetone (t 50/1
1/1) thu c 4 phn on chnh l V-E1 (33,0 g), V-E2 (8,2 g), V-E 3 (8,0 g), V-E
4 (37,0 g).
V-E1 (33,0 g) c ha tan vi mt lng ti thiu ethyl acetate sau tm
vo 70,0 g silica gel, ct thu hi dung mi cho n khi thu c hn hp bt kh
ti. Tin hnh phn tch bng ct silica gel pha thng sau ra gii vi gradient
h dung mi n-hexane/acetone ( 8/1 10/1) thu c 4 phn on chnh l V-E1A
(15,0 g), V-E1B (3,0 g), V-E1C (2,1 g), V-E1D (18,0 g).
V-E1A c phn tch trn ct nhi silicagel pha thng vi h dung mi nhexane/ethyl acetate (1/1) thu c ba phn on V-E1A1 (2,0 g), V-E1A2 (3,7 g),
V-E1A3 (2,0 g). V-E1A2 tip tc c phn tch trn ct silicagel pha o (YMC
RP 18) vi h dung mi acetone/nc (5/1) thu c hp cht TG17 (10 mg). VE1A3 c phn tch trn ct nhi silicagel pha o vi h dung mi acetone/nc
(3/1) thu c hp cht TG9 (9 mg). V-E1D c phn tch trn ct silicagel pha
thng vi h dung mi n-hexane/ethyl acetate (6/1) thu c bn phn on VE1D1 (1,0 g), V-E1D2 (4,6 g), V-E1D3 (1,8 g), V-E1D4 (2,0 g). Sau , t VE1D2 tip tc c phn tch trn ct nhi silicagel pha o vi h dung mi
methanol/acetone/nc (3/1/1) thu c hp cht TG18 (11 mg), TG19 (13 mg),
TG20 (10 mg). V-E1D3 c phn tch trn ct nhi silicagel pha o vi h dung
mi acetone/methanol/nc (1/8/2), thu c hp cht TG3 (9 mg), TG6 (11 mg).
V-E2 (8,2 g) c phn tch trn ct sc k silica gel pha thng vi h
dung mi ra gii l n-hexane/acetone/ethyl acetate (30/1/1) thu c hp cht
TG10 (13 mg) v TG24 (8 mg).
42
Hnh 3. S phn lp cc hp cht t mu v cy du du l nhn.

43
V-E4 c phn tch trn ct silica gel pha thng vi h dung mi ra gii
chloroform/methanol (30/1) thu c bn phn on V-E4A (11,0 g), V-E4B (6,3
g), V-E4C (2,8 g), v V-E4D (3,2 g). T V-E4A tip tc phn tch trn ct silica
gel pha thng vi h dung mi n-hexane/acetone (4/1) thu c ba phn on VE4A1 (2,0 g), V-E4A2 (3,6 g), V-E4A3 (1,6 g). V-E4A2 c phn tch trn ct
sc k silica gel pha thng vi h dung mi ra gii l n-hexane/ethyl acetate (2/1)
thu c hp cht TG2 (11 mg) v TG4 (8 mg). V-E4B c phn tch trn ct
nhi silica gel pha thng vi h dung mi ra gii n-hexane/ethyl acetate (2/1) thu
c bn phn on V-E4B1 (2,5 g), V-E4B2 (2,6 g), V-E4B3 (2,4 g) v V-E4B4
(2,0 g). V-E4B1 c phn tch trn ct sc k silica gel pha thng vi h dung
mi ra gii l chloroform/acetone (15/1) thu c hp cht TG25 (10 mg).
Lp nc (V-N) c cho chy qua ct sc k trao i ion vi cht hp ph
l diaion HP-20 v h dung mi ra gii tng dn nng methanol trong nc (0,
25, 50, 75 v 100%) thu c bn phn on V-N1, V-N2 (21 g), V-N3 (12 g), VN4 (15 g) V-N5 (8 g). V-N2 phn tch trn ct silicagel pha thng vi h dung
mi chloroform/methanol (15/1) thu c hp cht TG26 (7 mg). Phn on V-N4
(31 g) c phn tch bng sc k ct silica gel pha thng ra gii bng h dung
mi n-hexane/acetone (2/1) thu c hai hp cht TG5 (15 mg) v TG7 (7 mg).
3.2. HNG S VT L V D LIN PH CA CC HP CHT PHN
LP C T CY DU DU L NHN
3.2.1. Hp cht TG1 (hp cht mi): Tetraglabrifolioside
Cht bt mu trng.
Nhit nng chy: 192-194oC.
quay cc: []25
= +32,1 (c = 0,3, MeOH).
HR-ESI-MS: m/z 379,1609 ([MH]).
Tnh ton l thuyt cho cng thc C16H27O10: 379,1604.

CTPT: C16H28O10; KLPT M = 380.
S liu ph 1H- NMR v 13C-NMR (CD3OD): xem bng 8.
3.2.2. Hp cht TG2: 6-Acetonyl-N-methyldihydrodecarine
Cht bt v nh hnh, mu nu.
44

quay cc: []25
= -9,3 (c = 0,02, CHCl3).
HR-ESI-MS: m/z 392,1493 ([M+H]+).
Tnh ton l thuyt cho cng thc C23H22NO5: 392,1498.

CTPT: C23H21NO5; KLPT M = 391.
S liu ph 1H-NMR v 13C-NMR (DMSO-d6): xem bng 9.
3.2.3. Hp cht TG3: 6-Acetonyldihydrochelerythrine
quay cc: []25
= -128,2 (c = 0,02, CHCl3).
HR-ESI-MS: m/z 406,1654 ([M+H]+).
Tnh ton l thuyt cho cng thc C24H24NO5: 406,1654.

S liu ph 1H-NMR v 13C-NMR (CDCl3): xem bng 10.
3.2.4. Hp cht TG4: Decarine
Cht dng tinh th hnh kim, mu vng.
3.2.5. Hp cht TG5: Iwamide
3.2.6. Hp cht TG6: Rutaecarpine
Cht bt dng v nh hnh, mu vng.
HR-ESI-MS: 288,1107 ([M+H]+).
Tnh ton l thuyt cho cng thc C18H14N3O (288,1131).
CTPT: C18H13N3O; KLPT M = 287.
45
3.2.7. Hp cht TG7: 12-Hydroxyevodol

Cht bt dng v nh hnh mu vng nht.
quay cc: []25
= -113,7 (c = 0,5, MeOH).
3.2.8. Hp cht TG8: Rutaevine

Cht dng tinh th mu khng mu.
quay cc: []25
= -149,6 (c = 0,005, CHCl3).
CTPT: C26H30O9; M = 486.
3.2.9. Hp cht TG9: Lupeol

Cht dng tinh th mu trng.
quay cc: []25
= +26,4 (c =0,5 CHCl3).
CTPT: C30H50O; KLPT M= 426.
3.2.10. Hp cht TG10: Friedelan-3-one

Cht dng tinh th mu trng.
quay cc: []25
= +29,5 (c =0,1 CHCl3).
CTPT: C30H50O; KLPT M=426.
3.2.11. Hp cht TG11: Phellamurin

Cht rn, mu vng.
Nhit nng chy 204-205oC.
quay cc: []25
= -21,4 (c =0,2 MeOH).
CTPT: C26H28O11; KLPT M =518.

46
3.2.12. Hp cht TG12: Epimedoside C

Cht dng tinh th hnh kim mu vng.
Nhit nng chy: 289oC.
quay cc: []25
= -92,4 (c =0,05, MeOH).
CTPT: C26H28O11; KLPT M=516.
3.2.13. Hp cht TG13: Astragalin

Cht tinh th hnh kim, mu vng.
Nhit nng chy 178-179oC.
quay cc: []25
= +16,9 (c =0,65, MeOH)
ESI-MS: m/z 477 [M+H]+ v 471 [M+Na]
CTPT: C21H20O11; KLPT M =448;
3.2.14. Hp cht TG14: Nicotiflorin
quay cc []25
= +20,2 (c = 0,5, MeOH);
3.2.15. Hp cht TG15: Trifoline

quay cc: []25
= +17,6 (c =0,5, MeOH).
CTPT: C21H20O11; KLPT M=448.
3.2.16. Hp cht TG16: Quercetin

CTPT: C15H10O7; KLPT M= 302.
S liu ph 1H-NMR v 13C-NMR (CD3OD): xem bng 23.
47
3.2.17. Hp cht TG17: -Tocopherol

Cht dng du, mu vng.
o
quay cc []25
= +26,4 (c= 0,5, CHCl3).
3.2.18. Hp cht TG18: N-Isobutyl-2E,4E-tetradecadienamide

Cht dng du, khng mu.
HR- ESI-MS: m/z 280,2640 [M+H]+.
Tnh ton l thuyt cho cng thc C18H34NO: 280,2640.
CTPT: C18H33NO; KLPT M = 279.
3.2.19. Hp cht TG19: N-Isobutyl-2E,4E-decadienamide
Cht bt mu trng.
CTPT: C14H25NO; KLPT M = 223.
3.2.20. Hp cht TG20: N-Isobutyl-2E,4E,8E-tetradecatrienamide
Cht dng du, khng mu;
HR ESI-MS: m/z 278,2483 [M+H]+.
Tnh ton l thuyt cho cng thc C18H32NO: 278,2483.
CTPT: C18H31NO; M = 277.
3.2.21. Hp cht TG21: Syringin
Tinh th mu trng.
o
quay cc []25
= 20,2 (c= 0,5, MeOH).
3.2.22. Hp cht TG22: Saikolignannisode A

Cht bt mu vng nht.
48
quay cc []25
= +25,3 (c = 0,5, MeOH);

3.2.23. Hp cht TG23: Picraquassioside D
Cht bt mu trng.
quay cc []25
= 70,4 (c =0,5, MeOH).
ESI-MS: m/z 303 [M+H]+.
CTPT: C13H18O8 v M= 302.

3.2.24. Hp cht TG24: Stigmatsterol
Cht dng tinh th hnh kim mu trng.
quay cc: []25
= -54,2 (c = 1,9 CHCl3).
Nhit nng chy: 170oC.
ESI-MS: m/z: 395,3 [M -H2O+H]+.
Tnh ton l thuyt cho cng thc: C29H48O.

CTPT: C29H48O, KLPT M= 412,00.
3.2.25. Hp cht TG25: Daucosterol
Cht bt mu trng.
quay cc: []25
= -41,2 (c = 1,9 CHCl3).
ESI-MS: m/z: 397,3 [M -C6H12O6+H]+.
Tnh ton l thuyt cho cng thc: C35H60O6.

CTPT: C35H60O6; M = 576.
3.2.26. Hp cht TG26: 5-Hydroxymethylfurfural
Cht dng du mu vng.
49
CHNG 4
KT QU V THO LUN
4.1. PHN LP CC HP CHT T CY DU DU L NHN
Nhm xc nh thnh phn ha hc v tc dng dc l ca cy du du l
nhn, chng ti tin hnh cc nghin cu ha hc v xc nh hot tnh sinh hc ca
cc cht phn lp c.
phn lp cc hp cht t cy du du l nhn, u tin p dng phng
php chit lng-rn. S dng dung mi chit c phn cc trung bnh l methanol
vi mc ch kho st c cc hp cht c phn cc t n kh phn cc. Trong
qu trnh chit, kt hp s dng nhit v siu m nhm rt ngn thi gian chit
v tng hiu sut chit. Cc phn on th thu c bng cch s dng phng
php chit phn b lng-lng vi vic s dng cc dung mi khng tan vo nhau v
phn b cht vo cc pha khc nhau. Dung mi chit c tng dn phn cc t
t phn cc n phn cc nhiu: chloroform ethyl acetate nc. Qu trnh lm
giu cht c kim tra bng sc k lp mng trc khi tin hnh phn tch bng
cc loi sc k ct vi cc loi cht hp ph khc nhau.
Vic phn lp cc hp cht s dng cc cht php ph khc nhau nhm tng
kh nng tch. i vi nhng hn hp kh c kh nng tch trn sc k pha thng,
s dng silica gel pha o vi chiu di mch cht hp ph khc nhau (RP-8 hoc
RP-18) nhm tng thm kh nng tch. Trong qu trnh tch, kim tra v la chn
h dung mi kim tra trn sc k lp mng v trn ct c ging nhau v la chn
chiu di ct, ng knh ct ph hp vi khi lng cht cn tch cng nh Rf ca
tng cht trong hn hp.
Cc dch chit phn on ca mi phn on c xc nh s b thnh phn
ha hc bng sc k lp mng. Trn c s kt qu kim tra sc k bn mng ca
dch chit phn on ethyl acetate c nhiu vt cho thy thnh phn ha hc chnh
ca cy du du l nhn. Kim tra so snh chloroform, nhn thy cc vt trn sc k
lp mng ging vi cc vt trn dch ethyl acetate. V vy cc dch chit ca phn
on chloroform khng c nghin cu su hn. Chnh v vy, vic phn lp cc
hp cht tp trung vo phn phn on ethyl acetate v phn nc.
50
4.2 XC NH CU TRC CC HP CHT

4.2.1. Hp cht TG1 (cht mi): Tetraglabrifolioside
O
6''
OH
OH
6''
OH
COOH
COOH
O
1''
5''
'
OH
'
6'
5'
5''
6'
HO
HO
3''
1''
O
2
1'
HO
HO
5'
HO
HO
O
2'
OH
OH
1'
OH
HO
TG1
TG1a
Hnh 4. Cu trc ha hc v cc tng tc HMBC chnh ca TG1

v cu trc ha hc ca hp cht tham kho TG1a.
Hnh 5. Ph HR-ESI-MS ca TG1.

Hp cht TG1 c phn lp di dng cht bt mu trng. Cng thc phn
t c xc nh l C16H28O10. Da trn ph khi lng phn gii cao HR ESI MS
(Hnh 5) xut hin pic ion gi phn t ti m/z 379,1609 ([MH]) (tnh ton l
thuyt cho cng C16H27O10: 379,1604).
Trn ph 1H-NMR ca TG1 xut hin tn hiu ca mt proton anome ti H
4,34 (d, J = 8,0 Hz), mt nhm methyl bc 3 ti H 1,36 (s), mt nhm methyl bc 2
ti H 1,21 (d, J = 6,5 Hz) v mt nhm methyl bc mt ti H 0,96 (t, J = 7,5 Hz).
Ph 13C-NMR (Hnh 9) v DEPT (Hnh 10) ca TG1 cho thy s xut hin ca hai
nhm cacbonyl ti C 172,63 (C-1) v 178,50 (C-5), mt cacbon bc bn ti
51
70,88 (C-3), 6 nhm oxymethine ti C 71,74 (C-4), 75,05 (C-5), 75,26 (C-2),
77,92 (C-3), 79,07 (C-2) v 103,93 (C-1); bn nhm methylen ti C 30,25 (C-3),
46,99 (C-2), 47,26 (C-4) v 64,73 (C-6); ba nhm methyl ti C 9,98 (C-4), 21,48
(C-1) v 27,81 (C-6). Cc tn hiu cacbon ti C 103,93 (C-1), 75,26 (C-2),
77,92 (C-3), 71,74 (C-4), 75,05 (C-5) v 64,73 (C-6) cng vi hng s tng tc
ca proton JH-1-H-2 = 8,0 Hz ln, gi s c mt ca mt n v ng -Dglucopyranoside. xc nh chnh xc phn ng, hp cht TG1 c thy phn
trong mi trng acid thu phn ng; sau thc hin phn ng vi
trimethylsilylimidazole. C quay sn phm phn ng v ri chit phn lp bng nhexane/nc thu c phn lp n-hexane. Lp n-hexane ny c phn tch trn
my GC vi iu kin: ct SPB-1 (0,25 mm 30 m); detector FID, nhit ct
210 C, nhit bung bm 270 C, nhit bung bm 300 C, kh mang heli
(tc dng 2 mL/pht) thu c mt pic tn hiu ti thi gian lu 14,11 pht.
Tin hnh tng t cho cc mu chun D-glucose v L-glucose thu c thi gian
lu ca persilylated D-glucose v L-glucose ln lt l 14,11 v 14,26 pht. Bng
cc so snh thi gian lu, chng ti xc nh c chnh xc phn ng trong
hp cht TG1 l D-glucose. Trn ph HMBC (Hnh 12) thy c tng tc gia H
1,36 (s) vi C-3 (C 70,88)/C-2 (C 46,99)/C-4 (47,26); proton ca nhm
methylen ti H 2,64 (d, J = 15,0 Hz)/2,68 (d, J = 15,0 Hz) vi C-3 (C 70,88)/C1 (C 172,63); proton ca nhm methylen ti H 2,48 (d, J = 15,0 Hz)/2,59 (d, J =
15,0 Hz) vi C-3 (C 70,88)/C-4 (C 178,50) khng nh s tn ti ca mt nhnh
3-hydroxy-3-methylglutaric acid [118]. Cc tn hiu cn li trn ph c trng cho
nhm 2-butyl vi cc tn hiu ca hai nhm methyl ti C-1 (C 21,48)/H 1,21 (d, J
= 6,5 Hz) v C-4 (C 9,98)/H 0,96 (t, J = 7,5Hz); mt nhm methylen ti C 30,25
(C-3)/H 1,50 (m) v 1,62 (m) v mt nhm oxymethine ti C-2 (C 79,07)/H 3,74
(m) v c khng nh thm bng cc tng tc trn ph HMBC. Tng tc
HMBC gia proton anome H-1 (H 4,34) v C-2 (C 79,07); gia H-2 (H 3,74) v
C-1 (C 103,93) cho php khng nh nhm 2-butyl lin kt vi C-1 ca ng qua
cu oxy. V tr este ha ca nhnh glutaric acid ti C-6 c khng nh bi tng
tc gia cc proton H-6 (H 4,21 v 4,45) v cacbonyl C-1 (C 172,63).
52
T cc bng chng ph nu trn, hp cht TG1 c xc nh l 2-butyl-O-D-glucopyranosyl(16)-3-hydroxyl-3-methylglutaric acid. Cu hnh tng i ca

TG1, c xc nh trn c s s ph hp v gi tr dch chuyn ha hc 1H- v
C-NMR cng nh gi tr hng s tng tc ca cc proton ca TG1 vi cc s
13
liu ti cc v tr tng ng c cng b ca hp cht 1-[(2R)-4-(4hydroxyphenyl)-2-butanol-2-O--D-glucopyranosyl]-3-hydroxyl-3-methyl-glutaric

acid (TG1a) [119] l hp cht c cu trc tng t TG1 ch khc ch thay gc 2butanol bng gc (2R)-4-(4-hydroxyphenyl)-2-butanol.
Nh vy, TG1 c xc nh l (2R*,3S*)-2-butyl-O--D-glucopyranosyl
(16)-3-hydroxyl-3-methylglutaric acid, mt hp cht mi ln u phn lp t
thin nhin v c t tn l tetraglabrifolioside.
Bng 8. S liu ph NMR ca TG1 v hp cht tham kho
TG1a
C#
C
21,48
79,07
DEPT
CH3
CH
30,25
CH2
4
1
2
3
4
5
103,0
75,9
78,6
72,4
75,9
9,98
103,93
75,26
77,92
71,74
75,05
CH3
CH
CH
CH
CH
CH
65,5
64,73
CH2
173,6
172,63
48,0
46,99
CH2
71,7
70,88
48,7
47,26
CH2
5
6
180,9
28,7
178,50
27,81
C
CH3
C
1
2
TG1
H (J = Hz)
1,21 (d, 6,5)
3,74 (m)
1,50 (m)
1,62 (m)
0,96 (t, 7,5)
4,34 (d, 8,0)
3,18 (t, 8,5)
3,36*
3,33*
3,47 (m)
4,21 (dd, 6,0, 11,5)
4,45 (dd, 1,5, 11,5)
2,64 (d, 15,0)
2,68 (d, 15,0)
2,48 (d, 15,0)
2,59 (d, 15,0)
1,36 (s)
HMBC (H C)
2, 3
1, 4, 3
1, 2, 4
2, 3
2, 3
1, 3, 4
2, 4, 5
2, 3, 5, 6
1, 3, 5, 6
1, 4, 5
1, 4, 5
1, 3, 4, 6
2, 3, 5, 6
2, 3, 5, 6
2, 3, 4
C ca 1-[(2R)-4-(4-hydroxyphenyl)-2-butanol-2-O--D-glucopyranosyl]-3-hydroxyl-3methylglutaric acid [119], * tn hiu chp
53
Hnh 6. Ph 1H-NMR ca TG1.
Hnh 7. Ph 1H-NMR gin (a) ca TG1.

54
Hnh 8. Ph 1H-NMR gin (b) ca TG1.
Hnh 9. Ph 13C-NMR ca TG1.

55
Hnh 10. Ph DEPT ca TG1.
Hnh 11. Ph HSQC ca TG1.

56
Hnh 12. Ph HMBC ca TG1.
Hnh 13. Sc k ca cc dn xut TMS ca D-glucose, L-Glucose v TG1.

57
4.2.2. Hp cht TG2: 6-Acetonyl-N-methyldihydrodecarine

12
12a
11
4a
10
2
3
4
10a
6a
HO
O
H 3C
4b
10b
N
CH3
N
CH3
HO
1'
2'
3'
H 3C
CH3
CH3
Hnh 14. Cu trc ha hc v cc tng tc HMBC chnh ca TG2.

Hp cht TG2 thu c di dng bt v nh hnh, mu nu. Trn ph khi
lng phn gii cao HR ESI MS (Hnh 15) xut hin pic ion gi phn t ti m/z
392,1494 ([M+H]+) (tnh ton l thuyt cho cng thc C23H22NO5: 392,1498) cho
php xc nh cng thc phn t ca TG2 l C23H21NO5. Ph 1H-NMR (Hnh 16)
ca TG2 xut hin tn hiu ca 6 proton thm trong cc tn hiu ti H 7,29 (1H,
s) v 7,32 (1H, s), gi s c mt ca vng thm c hai proton nm v tr para; 2
cp tn hiu ti H 6,91 (d, J = 8,5 Hz) v 7,50 (d, J = 8,5 Hz); 7,54 (d, J = 8,5 Hz)
v 7,76 (1H, d, J = 8,5 Hz) gi 2 cp proton vng thm dng doublet nm v tr
ortho. Ngoi ra, cn c s xut hin tn hiu ca 1 nhm dioximethylene ti H 6,11
(br s) v 6,14 (br s); 1 nhm methoxy ti H 3,96 (s); 1 nhm N-methyl ti H 2,61
(s); 1 nhm N-methine ti H 4,90 (dd, J = 5,5, 10,5 Hz).
Ph 13C-NMR v DEPT (Hnh 19) ca TG2 xut hin tn hiu ca 23 nguyn
t cacbon trong c 11 cacbon bc bn, 7 methine, 3 methyl v 2 methylene. Phn
tch d liu ph thy tn hiu ca nhm acetonyl ti C 29,99 (C-3), 47,02 (C-1) v
206,37 (C-2); 1 nhm methoxy ti C 60,10; 1 nhm N-methyl ti C 42,38.
Trn ph HMBC (Hnh 21) thy c cc tng tc gia H-6 (H 4,90) vi C-1
(C 47,02)/C-2 (C 206,37); tng tc gia H-3 (H 2,10) vi C-1 (C 47,02)/C-2
(C 206,37) cho thy nhm acetonyl gn ti C-6. Cc tng tc HMBC ca nhm
methoxy H 3,96 (7-OCH3) vi C-7 (C 143,96) v tng tc gia proton ca nhm
hydroxyl (H 9,63) vi C-7 (C 143,96)/C-8 (C 149,75)/C-9 (C 116,01) cho php
58
xc nh nhm methoxy v hydroxy ln lt ti cc v tr C-7 v C-8. chuyn

dch ha hc 13C-NMR ca C-7 (C 143,96) v C-8 (C 149,75) c xc nh chnh
xc bng ph cng hng t hai chiu vi s xut hin ca cc tng tc HMBC
gia H-6 (H 4,90) vi C-7 (C 143,96); gia H-10 (H 7,50) vi C-8 (C 149,75).
C
1
2
3
4
4a
4b
6
6a
7
8
9
10
10a
10b
11
12
12a
1
C#
104,4
148,5
147,5
100,5
123,9
138,8
54,8
123,3
151,3
144,9
115,1
119,7
131,0
127,5
120,0
124,7
127,2
46,5
2
3
OCH2O
207,6
31,5
101,1
7-OCH3
N-CH3
8-OH
61,9
42,4
#
DEPT
H (J=Hz)
C
104,13 CH
7,29 (s)
147,70 C
147,05 C
99,45 CH
7,32 (s)
123,22 C
138,09 C
54,35 CH
4,90 (dd, 5,5, 10,5)
122,28 C
143,96 C
149,75 C
116,01 CH
6,91 (d, 8,5)
118,92 CH
7,50 (d, 8,5)
130,33 C
127,58 C
119,63 CH
7,76 (d, 8,5)
123,72 CH
7,54 (d, 8,5)
126,54 C
47,02 CH2 2,22 (dd, 5,5, 15,5)
2,24 (dd, 10,5, 15,5)
206,37 C
29,99 CH3 2,10 (s)
101,11 CH2 6,11 (br s)
6,14 (br s)
60,10 CH3 3,96 (s)
42,38 CH3 2,61 (s)
9,63 (s)
HMBC (HC)
2, 12a
2, 4b
4b, 6a, 7, 1, 2
7, 8
6a, 8, 10b
4b, 10a
12a, 4a, 1
1, 2
2, 3
7
4b, 6
7, 8, 9
C ca 6-acetonyl-N-methyl-dihydrodecarine o trong CDCl3 [120].
Cc gi tr C ca C-7 v C-8 cng b trong lun n khc vi trong ti liu

tham kho [120] ( dch chuyn ha hc ca C-7 v C-8 b o v tr) c th do
Carromberth v khng s dng ph cng hng t hai chiu trong qu trnh xc
nh cu trc nn gn nhm gi tr C ca C-7 v C-8 vi nhau. Cc tng tc
59
HMBC gia H-9 (H 6,91)/H-10 (H 7,50) vi C-8 (C 149,75); gia H-11 (H 7,76)
vi C-10a (C 130,33)/ C-4b (138,09); gia H-12 (H 7,54) vi C-1 (C 104,13)/ C4a (C 123,22)/ C-12a (C 126,54); gia H-1 (H 7,29) vi C-2 (C 147,70)/C-12a
(C 126,54)/C-12 (C 123,72); gia proton dioximethylen -OCH2O- (H 6,11 v
6,13) vi C-2 (C 147,70)/ C-3 (C 147,05) cho php xc nh chnh xc chuyn
dch ha hc ca cc nguyn t cacbon trong khung benzophenanthridine.
T nhng d kin ph trn, kt hp vi so snh s liu ph
13
C-NMR ca
TG2 vi hp cht 6-axetonyl-N-methyl-dihydrodecarine thy ph hp tt c cc

v tr tng ng [120]. c bit xc nh lp th ti v tr C-6, so snh
chuyn dch ca C-6 v C-1 cng nh hng s tng tc J ca H-6 v H-1 vi v
tr tng ng ca hp cht 6-axetonyl-N-methyldihydrodecarine ta thy hon ton
ging nhau. V vy, hp cht TG2 c khng nh l 6-axetonyl-Nmethyldihydrodecarine, mt hp cht phn lp t loi Zanthoxylum
riedelianum [120], nhng y l ln u tin hp cht ny c phn lp c t
chi Tetradium.
Hnh 15. Ph HR-ESI-MS ca hp cht TG2.
60
Hnh 17. Ph 1H-NMR gin ca TG2.

61

62

63
4.2.3. Hp cht TG3: 6-Acetonyldihydrochelerythrine

12
11
10
9
4a
6a
7
O
O
2
3
4
10a
CH3
H 3C
4b
10b
12a
5N
1'
N
CH3
CH3
2'
3'
CH3
O
H 3C
CH3
CH3

Hp cht TG3 thu c di dng bt mu nu v hin mu vng trn bn TLC
khi dng thuc th Dragendorff cho thy y cng l mt hp cht alkaloid. Trn ph
khi lng phn gii cao HR ESI MS ca hp cht TG3 (Ph lc 1) xut hin pic ion
gi phn t ti m/z 406,1654 ([M+H]+) (tnh ton l thuyt cho cng thc C24H24NO5:
406,1655) cho php kt lun cng thc phn t ca TG3 l C24H23NO5.
Ph 1H-NMR ca TG3 xut hin tn hiu ca su proton thuc vng thm
trong hai tn hiu dng singlet ti H 7,10 (s) v 7,52 (s); hai cp tn hiu dng
doublet u c hng s tng tc ln ti H 6,96 (d, J = 8,5 Hz) v 7,53 (d, J = 8,5
Hz); 7,48 (d, J = 8,5 Hz) v 7,71 (d, J = 8,5 Hz) l tn hiu ca hai proton vng
thm dng singlet nm v tr para vi nhau v 2 cp proton vng thm dng
doublet v tr ortho. Trn ph cn quan st thy tn hiu ca mt nhm
dioxymethilen (-OCH2O-) ti H 6,03 (d, J = 1,0 Hz) v 6,04 (d, J = 1,0 Hz), 2
nhm methoxy ti H 3,93 (s) v 3,96 (s); mt nhm N-methyl ti H 2,64 (s) v 1
nhm N-methine ti H 5,05 (dd, J = 5,5, 11,0 Hz). S c mt ca mt nhm
acetonyl ti C-6 ca khung benzophenanthridine c xc nh bi s xut hin tn
hiu ca 1 nhm methyl ti H 2,06 (s), 1 nhm methylen ti H 2,26 (dd, J = 5,0,
15,0 Hz)/2,58 (dd, J = 11,5, 15,0 Hz).
Ph 13C-NMR v ph DEPT (Ph lc 1) ca TG3 xut hin tn hiu ca 24
cacbon trong c 11 cacbon bc bn, 7 nhm methine, 2 nhm methylen v 4
nhm methyl. Phn tch d liu ph thy tn hiu ca mt nhm acetonyl ti C
64
207,54 (C-2), 31,08 (C-3), 46,87 (C-1); tn hiu ca 2 nhm methoxy ti C 55,82
(8-OCH3) v 60,98 (7-OCH3); 1 nhm N-methyl ti C 42,82; v tn hiu ca khung
benzophenanthridine xc nh ti C 104,35 (C-1), 148,17 (C-2), 147,59 (C-3),
100,63 (C-4), 123,30 (C-4a), 138,90 (C-4b), 54,93 (C-6), 124,82 (C-6a), 145,57 (C7), 152,16 (C-8), 111,60 (C-9), 118,80 (C-10), 131,08 (C-10a), 128,19 (C-10b),
119,77 (C-11), 123,87 (C-12) v 127,35 (C-12a). Tng t nh hp cht TG2, Cc
gi tr C ca C-7 v C-8 ca TG3 cng b trong lun n khc vi cc gi tr trong
ti liu tham kho [120] ( dch chuyn ha hc ca C-7 v C-8 b o v tr) c
th do Carromberth v nhm nghin cu khng s dng ph cng hng t hai
chiu trong qu trnh xc nh cu trc nn gn nhm gi tr C ca C-7 v C-8
vi nhau. T cc phn tch s liu ph 1H- v 13C-NMR, cho thy TG3 cng l mt
hp cht benzophenanthridine v c s liu ph tng t nh TG2, ngoi tr s c
mt thm ca nhm methoxy ti C-8. Thng qua cc tng tc trc tip H-C trn
ph HSQC chuyn dch ha hc ca cc proton c gn cho cc cacbon tng
ng. Trn ph HMBC (Ph lc 1) thy c cc tng tc ca H-6 (H 5,05) v H-3
(H 2,06) vi C-2 (C 207,54)/C-1 (C 46,87) khng nh v tr ca nhm
acetonyl gn vo C-6 ca khung benzophenanthridine. Bn cnh , tng tc gia
nhm hai methoxy ti H 3,96 v 3,93 vi C-7 (C 145,57)/C-8 (C 152,16) cho
php xc nh v tr ca cc nhm methoxy ti C-7 v C-8. Cc tng tc gia H-9
(C 6,96)/ H-10 (7,53) vi C-8 (C 152,16); tng tc gia H-11 (H 7,71) vi cc
tn hiu C-10a (C 131,08)/ C-4b (138,90); tng tc gia proton H-12 (H 7,48) vi
cc cacbon C-1 (C 104,35)/ C-4a (123,30)/ C-12a (127,35); tng tc gia proton
H-1 (H 7,10) vi cc cacbon C-2 (C 148,17)/ C-12a (127,35)/ C-12 (123,87);
tng tc gia cc tn hiu proton ca OCH2O (H 6,03/6,04) vi C-2 (C 148,17)/
C-3 (147,59) cho php xc nh chnh xc v tr cc nguyn t cacbon ca khung
benzophenanthridine. Kt hp so snh cc d liu ph vi ti liu tham kho cho
php xc nh cu trc ca TG3 l 6-acetonyldihydrochelerythrine, mt hp cht
bit c phn lp t loi Zanthoxylum riedelianum [120]. y l ln u tin
hp cht ny c phn lp t chi Tetradium.
65

C
1
2
3
4
4a
4b
6
6a
7
8
9
10
10a
10b
11
12
12a
1
C
104,4
148,5
147,5
100,5
123,9
138,8
54,8
123,3
151,3
144,9
115,1
119,7
131,0
127,5
120,0
124,7
127,2
46,5
2
3
OCH2O
207,6
31,5
101,1
7-OCH3
8-OCH3
N-CH3
61,9
42,4
DEPT
H (J=Hz)
C
104,35 CH
148,17 C
7,10 (s)
147,59 C
100,63 CH
7,52 (s)
123,30 C
138,90 C
54,93 CH
5,05 (dd, 5,5, 11,0)
124,82 C
145,57 C
152,16 C
111,60 CH
6,96 (d, 9,0)
118,80 CH
7,53 (d, 8,5)
131,08 C
128,19 C
119,77 CH
7,71 (d, 8,5)
123,87 CH
7,48 (d, 8,5)
127,35 C
46,87 CH2
2,26 (dd, 5,0, 15,0)
2,58 (dd, 11,5 15,0)
207,54 C
31,08 CH3
2,06 (s)
101,04 CH2
6,03 (d, 1,0)
6,04 (d, 1,0)
60,98 CH3
3,96 (s)
55,82 CH3
3,93 (s)
42,82 CH3
2,64 (s)
HMBC (H C)
2, 12, 12a
2, 3, 4b
4b, 6a, 10a, 1
7, 8
8, 10b
4b, 10a
1, 12a, 4a
6, 2
1, 2
2, 3
7
8
4b, 6
C ca 6-Acetonyl-N-methyl-dihydrodecarine o trong CDCl3 [120].
4.2.4. Hp cht TG4: Decarine

12
12a
11
4a
10
4b
10b
2
3
4
10a
6a
8
7
HO
N
HO
O
H 3C
O
H 3C

Hp cht TG4 thu c di dng tinh th hnh kim, mu vng nu v hin
mu vng trn bn TLC khi dng thuc th Dragendorff cho thy y cng l mt
66
alkaloid.Trn ph 1H-NMR (Ph lc 2) ca TG4 xut hin tn hiu ca 7 proton

vng thm trong 3 tn hiu dng singlet ti H 7,51 (s), 8,53 (s) v 9,57 (s); 2 cp
tn hiu dng doublet ti H 7,58 (d, J = 8,5 Hz) v 8,46 (d, J = 8,5 Hz); 8,51 (d, J =
9,0 Hz) v 7,95 (d, J = 9,0 Hz); 1 nhm dioximethylen (-OCH2O-) ti H 6,21 (s); 1
nhm hydroxyl ti H 10,11 (s) v 1 nhm methoxy ti H 4,02 (s). Ph 13C-NMR
v ph DEPT (Ph lc 2) xut hin tn hiu ca 19 nguyn t cacbon trong c 10
cacbon bc bn, 7 cacbon methine, 1 cacbon methylen v 1 cacbon methyl. Thng
qua cc tng tc trc tip H-C trn ph HSQC chuyn dch ha hc ca cc
proton c gn vi cc cacbon tng ng. Trn ph HMBC thy c cc tng tc
gia 8-OH (H 10,11) vi C-7 (C 142,12)/ C-8 (147,76)/ C-9 (123,56); tng tc
gia cc proton ca nhm methoxy (OCH3) ti H 4,02 vi C-7 (C 142,12) cho
php khng nh v tr nhm hydroxy v methoxy ln lt ti C-8 v C-7. So snh
d liu ph NMR ca TG4 hon ton trng khp vi decarine, mt hp cht
c phn lp t loi Xanthoxylum madagascariense [121]. Nh vy, TG4 c
xc nh chnh xc l decarine.
HMBC (HC)
C
DEPT
H (J = Hz)
C#
C
1
104,4 104,47 CH
7,51 (s)
2, 3, 4a
2
148,1 148,10 C
3
147,9 147,87 C
4
100,8 100,86 CH
8,53 (s)
3
4a
128,4 128,27 C
4b
138,7 138,64 C
6
145,7 145,78 CH
9,57 (s)
4b, 6a, 10a
6a
121,4 121,59 C
7
142,1 142,12 C
8
147,5 147,46 C
9
123,5 123,56 CH
7,58 (d, 8,5)
7, 10a
10
118,5 118,61 CH
8,46 (d, 8,5)
6a, 8
10a
126,4 126,35 C
10b
120.0 119,99 C
11
118,5 118,70 CH
8,51 (d, 9,0)
4b, 10a, 12, 12a
12
127,0 127,04 CH
7,95 (d, 9,0)
10b, 4a, 1
12a
129,2 129,15 C
-OCH2O101,4 101,43 CH2
6,21 (s)
2, 3
7-OCH3
61,1
61,17 CH3
4,02 (s)
7
8-OH
10,11 (s)
7, 8, 9
#
C ca decarine, o trong DMSO [121].
67
4.2.5. Hp cht TG5: Iwamide

CH3
OH
O
11
15
14
2
3
1
CH3
OH
18
17
10
HO
6
13
12
4
16
N7
H 3C
CHO
HO
H 3C
CHO
Hnh 24. Cu trc ho hc v cc tng tc HMBC chnh ca TG5.

Hp cht TG5 thu c di dng bt v nh hnh, mu nu v hin mu
vng trn bn TLC khi dng thuc th Dragendorff cho thy y cng l mt alkaloid.
Ph 1H-NMR (Hnh 25) ca TG5 xut hin tn hiu ca 6 proton thuc vng thm ti
H 6,99 (s), 7,44 (s), 7,22 (d, J = 8,5 Hz), 7,79 (d, J = 8,0 Hz), 6,37 (d, J = 8,5 Hz) v
6,58 (d, J = 8,0 Hz); tn hiu ca 1 nhm dioximethylen (-OCH2O-) ti H 6,17 (d, J =
2,5 Hz); 1 nhm methoxy ti H 3,69 (s); 1 nhm N-methyl ti H 2,87 (s), 1 proton
ca nhm aldehyde ti H 7,94 (s), 2 nhm hydroxyl ti H 8,71(s) v 9,33 (s).
Ph 13C-NMR (Hnh 27) v ph DEPT (Hnh 28) ca TG5 xut hin tn hiu
ca 20 nguyn t cacbon trong c 10 cacbon bc bn, 7 cacbon methine, 1
cacbon methylen v 2 cacbon methyl. Tn hiu ca nhm cabonyl ti C 163,17 (C8) b dch chuyn v pha trng mnh do c th d on nhm cabonyl ny c
ni vi nit (-NCHO). Bn cnh , trn cc ph ny cn xc nhn tn hiu ca 1
nhm methoxy ti C 59,92 (11-OCH3) v 1 nhm N-methyl ti C 32,65.
Thng qua cc tng tc trc tip trn ph HSQC (Hnh 29) chuyn dch
ha hc ca cc nguyn t proton c gn vi cc cacbon tng ng. So snh cc s
liu ph NMR ca TG5 vi hp cht 10-O-demethyl-12-O-methylarnottianamide
[121] thy chuyn dch ha hc ti hu ht cc v tr ph hp tr chuyn dch
ha hc ti v tr C-12 (147,51 so vi 153,6). Kt hp vi cc phn tch trn c th
khng nh c s demethyl ha ti v tr C-12 ca hp cht 10-O-demethyl-12-Omethylarnottianamide. Cc tng tc HMBC chi tit c lit k trong Bng 12 v
Hnh 24. T nhng d liu trn kt hp so snh vi cc s liu c cng b
trong ti liu tham kho [122], hp cht TG5 c xc nh l iwamide, l mt
alkaloid ln u tin phn lp c t chi Tetradium.
68

C
1
2
3
4
5
6
8
9
10
11
12
13
14
15
16
17
18
N-CH3
-OCH2O10-OH
11-OCH3
12-OH
C
99,8
148,5
149,6
103,7
127,6
128,5
164,3
104,7
149,7
137,7
153,6
135,5
136,7
129,4
131,7
123,8
115,6
33,0
102,2
60,5
-
C
98,56
147,84
148,76
104,09
126,79
127,68
163,17
107,18
150,13
135,51
147,51
134,56
135,37
128,01
130,44
124,59
117,78
32,65
101,54
59,92
-
DEPT
CH
C
C
CH
CH
CH
CH
CH
C
C
C
C
C
C
C
CH
C
CH3
CH2
CH3
-
H (J=Hz)
6,99 (s)
7,44 (s)
7,79 (d, 8,0)
7,22 (d, 8,5)
7,94 (s)
6,37 (d, 8,5)
6,58 (d, 8,0)
2,87 (s)
6,17 (d, 2,5)
9,33 (s)
3,69 (s)
8,71 (s)
Gi tr #C ca iwamide o trong CDCl3 [122]

69
HMBC (H C)
2, 3, 16
3, 5,15
13, 16
13, 14, 18
NCH3
10, 18
10, 12, 13
8, 14
2, 3
11
11
18

70

71

4.2.6. Hp cht TG6: Rutaecarpine
10
11
8
12
9a
8a
12a
13a
N
H
14a
N
H
5
4a
1a
4
1

Hp cht TG6 thu c di dng bt v nh hnh, mu vng. Ph HR-ESIMS (Ph lc 3) xut hin pic ion ti v tr m/z 288,1107 ([M+H]+) (tnh ton l thuyt
cho cng thc C18H14N3O+: 288,1131) cho thy cng thc phn t ca TG6 l
C18H13N3O (M = 287). Ph 1H-NMR ca TG6 xut hin tn hiu ca 2 cacbon
methylen ti H 3,23 (t, J = 7,0 Hz), 4,59 (t, J = 7,0 Hz); 8 tn hiu ca proton thm ti
H 7,69 (d, J = 8,0 Hz), 7,71 (t, J = 8,0 Hz), 7,42 (t, J = 8,0 Hz), 8,32 (d, J = 8,0 Hz),
72
7,63 (d, J = 8,0 Hz), 7,18 (t, J = 8,0 Hz), 7,31 (t, J = 8,0 Hz), 7,37 (d, J = 8,0 Hz) v 1
proton ca nhm amin bc 2 ti H 9,46 (br s, NH). Ph 13C-NMR v ph DEPT ca
TG6 xut hin tn hiu ca 18 nguyn t cacbon, trong c 8 cacbon bc bn ti C
147,30 (C-1a), 121,15 (C-4a), 161,56 (C-5), 118,30 (C-8a), 125,68 (C-9a), 138,38 (C12a), 127,28 (C-13a) v 144,02 (C-14a); 8 cacbon methine ti C 126,51 (C-1), 134,38
(C-2), 126,26 (C-3), 127,28 (C-4), 120,12 (C-9), 120,68 (C-10), 125,68 (C-11), 112,13
(C-12); v 2 cacbon methylen ti C 41,16 (C-7), 19,69 (C-8) c trng cho khung
indolopyridoquinazolin. Tn hiu ca cacbonyl ti C 161,56 (C-5) dch chuyn v pha
trng mnh ti d on nhm cacbonyl lin kt trc tip vi nit.
C
1
1a
2
3
4
4a
5
7
8
8a
9a
9
10
11
12
12a
13a
14a
C#
126,7
147,6
134,3
126,2
127,3
121,2
161,6
41,1
19,7
118,3
125,7
120,1
120,7
125,6
112,1
138,2
127,2
144,9
C
126,51
147,30
134,38
126,26
127,28
121,15
161,56
41,16
19,69
118,30
125,68
120,12
120,68
125,68
112,13
138,38
127,27
145,02
#
DEPT
CH
C
CH
CH
CH
C
C
CH2
CH2
C
C
CH
CH
CH
CH
C
C
C
H (J=Hz)
7,69 (d, 8,0)
7,71 (t, 8,0)
7,42 (t, 8,0)
8,32 (d, 8,0)
4,59 (t, 7,0)
3,23 (t, 7,0)
7,63 (d, 8,0)
7,18 (t, 8,0)
7,31 (t, 8,0)
7,37 (d, 8,0)
-
HMBC (H C)
3, 4a
1a, 4
1, 4a
2, 5, 1a
5, 8, 8a, 14a
7, 8a, 9a, 13a
10, 11, 12a
9a, 11, 12
10, 12a
9a, 10
-
C ca rutaecarpine o trong CDCl3 [123].
Trn ph HMBC thy c tng tc gia H-2 (H 7,71)/H-4 (H 8,32) vi C-1a

(C 147,30); tng tc gia H-1 (H 7,69)/H-3 (H 7,42) vi C-4a (C 121,15) khng
nh v tr ca cc cacbon vng thm th nht. Cc tng tc gia H-4 (H 8,32)/H-7
(H 4,59) vi C-5 (C 161,56) xc nh v tr nhm cacbonyl ti v tr C-5. Bn cnh ,
tng tc gia H-8 (H 3,23) vi C-7 (C 41,16)/C-8a (118,30)/C-9a (125,68)/ C-13a
(127,27); tng tc gia H-9 (H 7,63) vi C-11 (C 125,68)/C-12a (138,38); tng tc
73
gia H-10 (H 7,18) vi C-11 (C 125,68)/C-12 (112,13)/C-9a (125,68) cho php xc

nh chnh xc v tr cc nguyn t cacbon ca khung indolopyridoquinazoline.
T nhng phn tch d kin ph ca TG6 kt hp vi so snh s liu ph NMR
ca hp cht rutaecarpine trong ti liu tham kho [123] thy ph hp tt c cc v tr
tng ng. Nh vy, hp cht TG6 c xc nh l rutaecarpine mt hp cht
c phn lp t loi Phellodendron amurense.
4.2.7. Hp cht TG7: 12-Hydroxyevodol
O
O
21
22
20
OH
OH
18
O
O
17
13
11
26
19
24
9
15
10
5
O
25
24
OH
OH

Hp cht TG7 thu c di dng bt v nh hnh, mu vng. Ph 1HNMR (Hnh 32) xut hin tn hiu proton ca 4 nhm oxymethine ti H 3,83 (br s),
4,06 (s), 4,08 (br s) v 5,46 (s); 2 nhm oxymethylen ti H 4,58 (d, J = 12,5 Hz) v
4,68 (d, J = 12,5 Hz); 4 nhm methyl bc ba ti H 0,86 (s), 0,91 (s), 1,35 (s) v
1,47 (s); v 3 proton olefin ti H 7,47 (s), 7,61 (s) v 6,49 (s) gi s c mt ca
vng furan th . Ph 13C-NMR (Hnh 35) v ph DEPT (Hnh 36) ca TG7 xut
hin tn hiu ca 26 nguyn t cacbon trong c 11 cacbon bc bn, 8 cacbon
methine, 3 cacbon methylen v 4 cacbon methyl. Nhng tn hiu trn ph NMR ca
TG7 gi y l mt hp cht c khung dng limonoid. V tr ca proton lin kt
trc tip vi cacbon tng ng c xc nh bng ph HSQC (Hnh 37). Cu trc
ca TG7 c khng nh da trn kt qu phn tch ph HMBC (Hnh 38). Cc
tng tc HMBC gia H-1 (H 4,08) vi C-3 (C 169,83)/C-19 (69,31); tng tc
gia proton Ha-2 (H 2,92)/ Hb-2 (H 2,78) vi C-1 (C 79,00)/ C-3 (C 169,83)/C-10
(C 46,87) cho php d on trong TG7 c vng ester ni phn t ti C-3/C-19.
74

1
2
C#
79,0
35,0
3
4
5
6
7
8
9
169,7
81,1
140,3
141,9
195,3
47,3
42,8
10
11
46,9
31,9
12
13
14
15
16
17
65,9
42,2
64,4
50,6
166,5
76,6
18
19
12,9
69,3
20
21
22
23
24
25
26
119,7
141,6
110,4
142,9
25,5
25,0
17,5
C DEPT
79,00 CH
34,95 CH2
169,83
81,12
140,30
141,93
195,32
47,29
42,88
C
C
C
C
C
C
CH
46,87 C
31,82 CH2
65,95
42,14
64,90
50,63
166,59
76,63
CH
C
C
CH
C
CH
12,91 CH3
69,31 CH2
119,74
141,71
110,45
142,93
25,54
25,03
17,05
C
CH
CH
CH
CH3
CH3
CH3
H (J = Hz)
4,08 (br s)
2,92 (dd, 2,0, 17,0)
2,78 (dd, 2,0, 17,0)
2,79 (d, 12,0)
1,90 (ddd, 4,5, 12,0, 14,0)
1,59 (d, 14,0)
3,83 (br s)
4,06 (s)
5,46 (s)
0,86 (s)
4,68 (d, 12,5)
4,58 (d, 12,5)
7,74 (s)
6,50 (s)
7,62 (s)
1,47 (s)
1,35 (s)
0,91 (s)
HMBC (HC)
3, 9, 19
1, 3, 10
1, 7, 8, 10, 11,
12, 19, 26
8, 9, 12, 13
14, 16
12, 13, 14, 18,
20, 21, 22
12, 13, 14, 17
1, 3, 9, 10
20, 22, 23
20, 21, 23
20, 21, 22
4, 5, 25
4, 5, 24
7, 8, 9, 14
C ca 12- hydroxyevodol o trong DMSO[3].
Cc nguyn t cacbon ca vng epoxy-lacton cng c xc nh thng qua

tng tc HMBC gia H-15 (H 4,06) vi C-14 (C 64,90)/ C-16 (C 166,59) v
gia H-17 (H 5,46) vi C-13 (C 42,14)/ C-14 (C 64,90)/ C-18 (C 12,91). Tng
tc gia proton methyl H-18 (H 0,86) vi C-12 (C 65,95)/ C-13 (C 42,14)/C-14
(C 64,90)/C-17 (C 76,63) cho thy c nhm hydroxy ti v tr C-12. Tng tc
HMBC gia H-21 (H 7,74) vi C-20 (C 119,74)/C-22 (C 110,45)/ C-23 (C
75
142,93); tng tc gia H-22 (H 6,50) vi C-20 (C 119,74)/ C-21 (C 141,71)/ C23 (C 142,93); tng tc gia proton H-23 (H 7,62) vi C-20 (C 119,74)/C-21 (C
141,71)/ C-22 (C 110,45) khng nh s c mt ca mt vng furan. Vng furan
ny c xc nh lin kt vi vng epoxy-lacton ti v tr C-17 thng qua cc
tng tc HMBC gia H-17 (H 5,46) vi C-20 (C 119,74)/ C-21 (C 141,71)/ C-22
(C 110,45).
Kt hp so snh cc d liu ph 1H- v 13C-NMR ca TG7 vi hp cht 12hydroxyevodol trong ti liu tham kho [3] cho thy c s ph hp ti tt c cc v
tr tng ng. c bit, cu hnh lp th ca H-12 c xc nh l thng qua vic
so snh chuyn dch cacbon v hng s tng tc J vi hp cht 12hydroxyevodol. T cc phn tch trn, hp cht TG7 c xc nh l 12hydroxyevodol, mt hp cht c phn lp t loi Tetradium rutacarpum
thuc chi Tetradium.
76

77

78

4.2.8. Hp cht TG8: Rutaevine
O
O
21
22
20
O
18
17
11
13
26
19
9
15
1
10
O
5
O
O
OH
OH
24
25

Hp cht TG8 thu c di dng tinh th khng mu. Ph 1H-NMR ca
TG8 (Hnh 40) xut hin tn hiu ca cc proton thuc 4 nhm oxymethine ti H
4,16 (s), 4,36 (s), 4,37 (s) v 5,50 (s); 1 nhm oxymethylen ti H 4,15 (d, J = 12,5
Hz ), 4,29 (d, J = 12,5 Hz); 4 nhm methyl bc ba ti H 0,65 (s), 1,22 (s), 1,37 (s)
v 1,44 (s); v 3 proton olefin ti H 6,38 (br s), 7,44 (br s) v 7,45 (s) gi s c
mt ca mt vng furan th .
79

80

81

Ph
13
C-NMR (Hnh 41) ca TG8 xut hin tn hiu ca 26 nguyn t
cacbon trong c 9 cacbon bc bn, 9 cacbon methine, 4 cacbon methylen v 4

cacbon methyl. Nhng tn hiu trn ph NMR ca TG8 gi y l mt hp cht
c khung dng limonoid. V tr ca proton lin kt trc tip vi cacbon tng ng
c xc nh bng ph HSQC (Hnh 43).
Cu trc ca TG8 c khng nh da trn kt qu phn tch ph HMBC
(Hnh 44). Cc tng tc HMBC gia H-18 (H 1,37) vi C-12 (C 31,97)/ C-13
(37,54)/ C-14 (65,47)/ C-17 (77,78) xc nh s c mt ca nhm methyl ti C-13;
tng tc gia H-26 (H 0,65) vi C-7 (C 81,46)/ C-8 (C 48,65)/ C-9 (C 45,60)/
C-14 (C 65,47) khng nh v tr ca nhm hydroxyl v methyl ln lt ti C-7 v
C-8. Ngoi ra, v tr ca nhm cacbonyl ti C-6 (C 206,81) c xc nh do c s
tng tc gia H-5 (H 3,12) vi C-6 (C 206,81). So snh cc d liu ph 1H- v
13
C-NMR ca TG8 thy s liu ph ca hp cht ny hon ton ph hp vi
rutaevine tt c cc v tr tng ng [3].T cc phn tch trn, c th khng nh

hp cht TG8 chnh l rutaevine, mt hp cht c phn lp t loi Tetradium
rutacarpum.
82

C
C#
81,9
C DEPT
82,68 CH
35,9
35,88
CH2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
170,9
81,4
64,5
207,2
81,4
48,6
45,3
45,6
19,3
31,0
37,2
65,9
50,8
166,9
77,5
20,5
169,98
82,34
63,61
206,81
81,46
48,65
45,60
46,02
19,66
31,97
37,54
65,47
50,77
166,89
77,78
20,97
C
C
CH
C
CH
C
CH
C
CH2
CH2
C
C
CH
C
CH
CH3
19
69,8
69,78
CH2
20
21
22
23
24
25
26
120,0
141,6
110,3
143,4
23,8
28,8
14,7
119,53
140,86
109,45
143,07
23,93
28,35
14,57
C
CH
CH
CH
CH3
CH3
CH3
H (J = Hz)
4,37 (br s)
2,64 (dd, 3,0, 16,0)
2,92 (dd, 3,0, 16,0)
3,12 (s)
4,36 (s)
2,79 (d, 12,5)
1,76 (m)/1,86 (m)
1,56 (m)/1,95 (m)
4,16 (s)
5,50 (s)
1,37 (s)
4,15 (d, 12,5)
4,29 (d, 12,5)
7,45 (s)
6,38 (br s)
7,44 (br s)
1,22 (s)
1,44 (s)
0,65 (s)
HMBC (HC)
2, 3
1, 3, 10, 19
4, 5, 10, 19, 25, 26

6, 9,
7, 8, 10, 11, 12, 19
9, 12
1, 3, 5
14, 16
13, 14, 18, 20, 21
13, 14, 17
12, 13, 26
20, 22, 23
20, 21, 22
20, 21, 22
4, 5, 26
4, 5, 25
7, 9, 14
C ca rutaevine o trong DMSO 90 MHz [3].
4.2.9. Hp cht TG9: Lupeol
30
29
20
19
21
22
18
12
25
11
26
13
17
16
14
9
1
2
10
HO
23
28
15
27
24
Hnh 45. Cu trc ha hc ca hp cht TG9.

83

C
DEPT
H (J = Hz)
C#
C
1
38,7
38,76
CH2
0,94 (m)/1,68 (m)
1,54 (m)/1,61 (m)
2
27,5
27,45
CH2
3
79,0
79,03
CH
3,19 (dd, 5,0, 11,5)
4
38,9
38,88
C
5
55,3
55,35
CH
0,69 (m)
1,39 (m)/1,54 (m)
6
18,3
18,35
CH2
7
34,3
34,33
CH2
1,25 (m)/1,41 (m)
8
40,9
40,88
C
9
50,5
50,49
CH
1,28 (m)
10
37,2
37,21
C
11
21,0
20,97
CH2
1,25 (m)/1,42 (m)
1,07 (m)/1,68 (m)
12
25,2
25,21
CH2
13
38,1
38,11
CH
1,67(m)
14
42,9
42,87
C
1,01 (m)/1,61 (m)
15
27,5
27,49
CH2
16
35,6
35,62
CH2
1,49 (m)/1,38 (m)
17
43,0
43,03
C
18
48,0
48,36
CH
1,36 (t, 12,5)
19
48,3
48,01
CH
2,38 (ddd, 6,0, 11,0, 11,0)
20
150,9
150,95
C
21
29,9
29,89
CH2
1,33 (m)/1,93 (m)
1,20 (m)/1,42 (m)
22
40,0
40,03
CH2
23
28,0
28,01
CH3
0,97 (s)
24
15,3
15,38
CH3
0,76 (s)
25
16,1
16,13
CH3
0,83 (s)
26
16,0
16,01
CH3
1,03 (s)
27
14,6
14,58
CH3
0,94 (s)
28
18,0
18,02
CH3
0,79 (s)
29
109,3
109,32
CH2
4,56 (br s)/4,68 (br s)
30
19,3
19,33
CH3
1,68 (s)
#
C ca lupeol o trong CDCl3 [124].
Hp cht TG9 thu c di dng kt tinh mu trng. Ph
13
C-NMR v
DEPT (Ph lc 4) ca TG9 xut hin tn hiu ca 30 nguyn t cacbon, trong c

6 cacbon bc bn, 6 cacbon methine, 11 cacbon methylen v 7 cacbon methyl c
trng cho mt hp cht triterpen khung lupan.S c mt ca nhm isopropenyl
c xc nhn bi 1 cacbon methyl ti C-30 (C 19,33) cng vi 1 lin kt i ti C
150,95 (C-20)/109,32 (C-29). Tn hiu ca 1 cacbon oxymethine ti C 79,03 (C-3)
cho php xc nhn c 1 nhm hydroxyl trong phn t ca hp cht TG9.
84
So snh s liu ph 1H- v 13C-NMR (Ph lc 4) ca hp cht TG9 vi hp

cht triterpen khung lup-20(29)-en bit l lupeol (3-hydroxylup-20(29)-en) nhn
c s ph hp tt c cc v tr tng ng (Bng 16). Nhn nh ny c khng
nh thm khi xem xt n hng s tng tc J ca proton H-3 ti H 3,19 (dd, J =
5,0, 11,5 Hz) vi hng s tng tc JH-2/H-3 ln, v vy H-3 v tr axial (a) hay , tc
l nhm OH ti C-3 c cu hnh equatorial (e) hay [124]. T cc phn tch nu trn,
hp cht TG9 c xc nh l 3-hydroxylup-20(29)-en hay lupeol.
4.2.10. Hp cht TG10: Friedelan-3-one
29
30
20
27
18
11
17
13
28
14
1
3
10
9
25
5
4
15
8
26
O
24
23

Hp cht TG10 thu c di dng cht kt tinh mu trng. Ph 1H-NMR
(Hnh 47) xut hin tn hiu ca 8 nhm methyl, trong c 7 nhm methyl bc 3
ti H 0,72 (3s), 0,87 (s), 1,01 (s), 1,00 (s), 1,18 (s), 1,05 (s) v 0,95 (s) v mt
nhm methyl bc 2 ti H 0,88 (d, J = 6,5 Hz) c trng cho mt hp cht c dng
tritecpenoid.Trn ph
13
C-NMR (Hnh 49) v DEPT (Hnh 50) xut hin tn hiu
ca 30 nguyn t cacbon, trong c 7 cacbon bc bn ti C 212,82 (C-3), 41,88

(C-5), 37,21 (C-9), 39,42 (C-13), 38,07 (C-14), 29,75 (C-17), 27,92 (C-20); 5 nhm
methine ti C-4 (C 57,94), C-8 (52,84), C-10 (59,21), C-12 (30,25), C-18 (42,58);
10 nhm methylen ti C 22,02 (C-1), 41,27 (C-2), 41,04 (C-6), 17,98 (C-7), 35,77
(C-11), 32,56 (C-15), 35,65 (C-16), 35,37 (C-19), 32,18 (C-21), 39,00 (C-22); 8
nhm methyl ti C 6,57 (C-23), 14,41 (C-24), 17,69 (C-25), 20,00 (C-26), 18,40
(C-27), 31,86 (C-28), 31,56 (C-29), 35,10 (C-30).
85
C
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30

HMBC (HC)
DEPT H (J =Hz)
C#
C
22,2
22,02 CH2
1,71(m)/1,96 (m)
2, 3, 5, 10
2,39 (dd, 4,0, 14,0)
41,5
41,27 CH2
1, 3, 10
2,28 (m)
213,1 212,82 C
58,2
57,94 CH
2,28 (m)
3, 5, 10, 23
42,1
41,88 C
41,3
41,04 CH2
1,28 (m)/1,72 (m)
5, 7, 8, 10, 24
18,2
17,98 CH2
1,36 (m)/1,49 (m
5, 6, 8, 9, 15
53,1
52,84 CH
1,38 (m)
7, 9, 14
37,4
37,21 C
59,5
59,21 CH
1,53 (m)
1, 2, 5, 6, 9, 25
35,6
35,77 CH2
1,26 (m)/1,45(m)
9, 12, 13
30,5
30,25 CH2
1,34 (m)
9, 11, 13, 14, 28
39,7
39,42 C
38,3
38,07 C
32,7
32,56 CH2
1,27 (m)/1,47 (m)
13, 15, 16, 17, 26
36,0
35,65 CH2
1,35 (m)/1,58 (m)
14, 15, 17, 18, 30
29,9
29,75 C
42,8
42,58 CH
1,56 (m)
13, 14, 16, 17, 19, 20
35,3
35,37 CH2
1,21 (m)/1,37 (m)
17, 18, 20, 21, 27
28,1
27,92 C
32,4
32,18 CH2
1,31 (m)/1,50 (m)
17, 19, 20, 22, 29
39,2
39,00 CH2
0,94 (m)/1,50 (m)
17, 18, 20, 21
6,81
6,57 CH3
0,88 (d, 6,5)
3, 4, 5
14,6
14,41 CH3
0,72 (s)
4, 5, 6, 10
17,9
17,69 CH3
0,87 (s)
8, 9, 10, 11
20,2
20,00 CH3
1,01 (s)
8, 13, 14, 15
35,0
35,10 CH3
0,95 (s)
12, 13, 14, 18
18,6
18,40 CH3
1,00 (s)
16, 17, 18, 22
31,7
31,56 CH3
1,05 (s)
19, 20, 21, 30
32,0
31,86 CH3
1,18 (s)
19, 20, 21, 29
#
C ca friedelan-3-one o trong CDCl3 [125].
Tn hiu ca nhm cacbonyl ti C 212,82 (C-3) v mt nhm methyl bc 2

ti C 6,57(C-23)/H 0,88 (d, J = 7,0 Hz) c trng cho nhm methyl lin kt vi C4 ca khung friedelan. T cc d kin ph nu trn cho php d on hp cht
TG10 l friedelan-3-one. So snh cc d kin ph ca TG10 vi hp cht friedelan3-one [125] thy hon ton trng khp. Nh vy, hp cht TG10 c khng nh
l friedelan-3-one, mt triterpenoid ln u tin phn lp c t chi Tetradium.
86

87

88

89
4.2.11. Hp cht TG11: Phellamurin

4"'
5''
3''
OH
OH
HO
1"'
6"
4'
O
HOHO
3"
1"
OH
O
7
OH
10
3
4
HO
1'
HO
HO
OH
OH
OH
OH

Hp cht TG11 thu c di dng tinh th mu vng. Trn cc ph 1H(Hnh 54) v 13C-NMR (Hnh 55) ca TG11 xut hin hai tn hiu ti H 7,31 (d, J
= 8,5 Hz) v 7,90 (d, J = 8,5 Hz) cng vi hai tn hiu cacbon methine c cng
cao gp i cc tn hiu khc ti C 129,18 v 114,84 gi s c mt ca mt vng
benzen th para. Bn cnh , cc tn hiu ti C 71,79 (C-3)/ H 4,57 (d, J = 11,0
Hz) v C 82,85 (C-2)/5,05 (d, J = 11,0 Hz); v tn hiu ca mt nhm cacbonyl ti
C 198,97 (C-4) chng t s tn ti mt hp cht flavan-3-ol.
Cc tng tc HMBC (Hnh 59) gia proton ca 5-OH (H 11,80) vi C-5
(C 160,96)/C-10 (C 101,83)/ v c bit vi cacbon methine C-6 (C 95,39);
tng tc gia proton H-6 (H 6,29) vi C-5 (C 160,96)/C-7 (C 163,14)/C-8 (C
108.95)/C-10 (C 101,83) chng t vng A th 5 v tr tr C-6. S c mt ca
mt phn t ng glucopyranosyl cng c xc nh bi cc c trng tn hiu
ph 1H-NMR proton anome ti H 4,91 (d, J = 7,5 Hz) cng vi cc tn hiu in
hnh trn ph 13C-NMR ti C 100,26 (C-1), C 73,28 (C-2), C 76,60 (C-3), C
69,63 (C-4), C 77,16 (C-5), C 60,64 (C-6). Hng s tng tc gia H-1 v H2 ln, JH-1/H-2 = 7,5 Hz gi y l lin kt O--glycoside. Phn t ng lin
kt vi flavanol ti C-7 do xut hin tng tc HMBC gia H-1 (H 4,91) v C-7
(C 163,14). S c mt ca nhm isopren c xc nh bi tn hiu ca 5 nguyn
t cacbon trn ph 13C-NMR (Hnh 56) ti C 21,29 (C-1), 122,35 (C-2), 130,30
(C-3), 25,48 (C-4), 17,50 (C-5). V tr ca nhnh ny lin kt trc tip vi C-8
c xc nh bi tng tc HMBC gia H-1 (H 3,01 v 3,26) v C-8 (C 108,95).
90

C
2
3
4
5
6
7
8
9
10
1
2,6
3,5
4
1
2
3
4
5
6
C#
82,9
71,8
199,1
160,9
95,4
163,2
108,9
158,6
101,8
127,6
129,2
114,8
157,6
100,03
73,3
76,6
69,6
77,2
60,6
C
82,85
71,79
198,97
160,96
95,39
163,14
108,95
158,63
101,83
127,61
129,18
114,84
157,61
100,26
73,28
76,60
69,63
77,16
60,64
21,3
21,29
CH2
2
3
4
5
122,4
130,3
25,5
17,5
122,35
130,30
25,48
17,50
CH
C
CH3
CH3
DEPT
CH
CH
C
C
CH
C
C
C
C
C
CH
CH
C
CH
CH
CH
CH
CH
CH2
H (J = Hz)
5,05 (d, 11,0)
4,57 (d, 11,0)
6,29 (s)
7,31 (d, 8,5)
7,90 (d, 8,5)
4,91 (d, 7,5)
3,27 (dd, 7,5, 9,0)
3,28 (t, 9,0)
3,16 (t, 9,0)
3,44 m
3,46 (dd, 2,5, 12,0)
3,71 (dd, 6,5, 12,0)
3,01 (dd, 7,5, 13,5)
3,26*
5,11 (t, 7,5)
1,57 (s)
1,50 (s)
HMBC (H C)
2, 4, 6
4, 1
5, 7, 8, 10
2, 4, 6, 2, 5
1, 3, 5, 4
7
1, 3, 4
1, 5
3
1, 4, 6
5
7, 8, 9, 2, 3
1, 4, 5, 8
2, 3, 5
2, 3, 5
Gi tr #C ca phellamurin ghi trong DMSO [126].
T cc phn tch trn, kt hp so snh d liu ph ca phellamurin c

phn lp t loi Phellodendron japonicum [126] thy tng ng tt c cc v tr.
Nh vy c th khng nh hp cht TG11 l phellamurin, hp cht ny ln u
phn lp c t chi Tetradium.
91

92

93

94
4.2.12. Hp cht TG12: Epimedoside C

4"'
5''
3''
OH
OH
HO
4'
O
HOHO
HO
1"'
6"
3"
1"
OH
OH
10
3
4
1'
HO
HO
OH
OH
OH
OH

Hp cht TG12 thu c dng tinh th hnh kim, mu vng. Ph 1H-NMR
(Ph lc 5) ca TG12 thy c xut hin tn hiu ca hai cp proton vng thm th
para ti H 6,94 (d, J = 9,0 Hz) v 8,05 (d, J = 9,0 Hz) v mt proton thm ti H
6,59 (s) cho php d on y l mt hp cht dng flavone. ng thi, trn ph
cn quan st thy tn hiu ca mt proton anome ti H 4,99 (d, J = 7,5 Hz) c
trng cho s c mt ca mt phn ng glycoside v s xut hin tn hiu ca mt
proton olefin ti H 5,21 (t, J = 7,0 Hz), hai nhm methyl bc ba ti H 1,62 (s) v
1,76 (s) cho php d on s c mt ca mt n v isopren.
Trn ph
13
C-NMR v DEPT xut hin tn hiu ca 26 nguyn t cacbon,
trong c 11 nguyn t cacbon bc 4, 11 nhm methine, 2 nhm methylene v 2

nhm methyl. Trong tn hiu c trng cho phn t ng glucose vi tn hiu
cacbon oximethine anome ti c 100,50 v 2 tn hiu c trng cho mt vng thm
th 1,4 ti c 129,55 v 115,49. S xut hin ca tn hiu cacbon methine ti c
97,43 v tn hiu cacbon bc 4 ti c 135,77 cho php khng nh s xut hin ca 1
nhm th ti v tr C-8 v s c mt ca nhm th hydroxy ti v tr C-3. V tr lin
kt ca phn t ng v nhnh isoprenyl c khng nh li da trn kt qu
phn tch ph 2 chiu HSQC v HMBC. Trn ph HMBC, thy xut hin tng tc
gia 2 tn hiu proton methilen ti H 3,43/3,64 (H-1) vi C-7 (c 160,07)/ C-8 (c
108,08)/ C-9 (c 152,70) cho php khng nh nhnh isoprenyl lin kt vi C-8.
95

C
2
3
4
5
6
7
8
9
10
1
2,6
3,5
4
1
2
3
4
5
6
C#
147,4
135,8
176,3
158,6
97,4
160,0
108,0
152,7
104,4
121,85
129,55
115,49
159,35
100,50
73,4
76,6
69,70
77,2
60,7
C
147,50
135,77
176,37
158,55
97,43
160,07
108,08
152,70
104,46
121,85
129,55
115,49
159,35
100,50
73,39
76,64
69,70
77,18
60,69
21,4
21,44
CH2
2
3
4
5
122,4
131,0
25,5
18,0
122,42
131,06
25,45
17,88
CH
C
CH3
CH3
DEPT
C
C
C
C
CH
C
C
C
C
C
CH
CH
C
CH
CH
CH
CH
CH
CH2
H (J = Hz)
6,59 (s)
8,05 (d, 9,0)
6,94 (d, 9,0)
4,99 (d,7,5)
3,32 (m)
3,31 (m)
3,17 (m)
3,42 (m)
3,46 (m)
3,71 (dd, 5,5, 11,5)
3,43*
3,64 (dd, 7,0, 14,5)
5,21 (t, 7,0)
1,62 (s)
1,76 (s)
HMBC (HC)
7, 8, 10
2, 4
1, 4, 3, 5
7
7, 8, 9, 2, 3
1, 4, 5
2, 3, 5
2, 3, 4
C ca epimedoside C [127], * tn hiu b trng lp.
Da vo tng tc gia tn hiu proton anome ca ng ti H 4,99 vi C-7

(c 160,07); tn hiu proton singlet 6.,59 vi C-5 (c 158,88)/ C-7 (c 160,07) /C-8
(c 108,08)/C-10 (c 104,46) cho php khng nh v tr lin kt ca phn t ng
vi C-7. S liu ph NMR ca TG12 ging vi s liu ph TG11 ngoi tr s xut
hin mt lin kt i ti C-2/C-3. T cc s liu ph, kt hp so snh vi ti liu
tham kho c cng b ca hp cht epimedoside C [127] thy hon ton ph
hp. T , cho php khng nh hp cht TG12 chnh l epimedoside C.
96
4.2.13. Hp cht TG13: Astragalin

OH
OH
4'
HO
1'
O
9
HO
6'
OH
OH
10
5
OH
HO
1''
OH
3"
OHO
6"
OH
OH
OH
OH

Hp cht TG13 thu c di dng tinh th hnh kim, mu vng. Ph khi
lng ESI-MS ca TG13 (Ph lc 6) xut hin tn hiu ti m/z 447 [M-H]-, gi
cng thc phn t ca hp cht ny l C21H20O11.
Trn ph 1H-NMR (Ph lc 6) ca TG13 xut hin cp tn hiu doublet ti
6,20 (d, J = 2,0 Hz) v 6,42 (d, J = 2,0 Hz) in hnh cho hai proton v tr C-6 v
C-8 ca vng A ca hp cht flavonol. Cp hai tn hiu doublet khc ti H 6,88
(dd, J = 1,5, 7,0 Hz) v 8,04 (dd, J = 1,5, 7,0 Hz) c trng cho vng thm B th
para. Tn hiu proton anome ti H 5,45 (1H, d, J = 7,5 Hz) gi trong TG13 c
mt 1 phn ng.
Ph
13
C-NMR (Ph lc 6) ca TG13 xut hin tn hiu ca 21 nguyn t
cacbon, trong c 6 tn hiu ti C 101,13 (C-1), 74,44 (C-2), 77,62 (C-3),

70,10 (C-4), 76,61 (C-5), 61,07 (C-6) khng nh s c mt ca phn ng
glucose v tn hiu ca 15 nguyn t cacbon thuc vo khung flavonol c vng B
th para. So snh cc d liu ph NMR ca TG13 vi hp cht kaempferol 3-O-D-glucopyranoside thy s ph hp hon ton [128]. Tng tc HMBC gia H-1
(C 5,45) v C-3 (C 133,44) gi phn O--D-glucopyranosyl ti C-3 ca flavonol.
Nh vy, c th khng nh hp cht TG13 l kaempferol 3-O--Dglucopyranoside, hp cht ny c tn gi l astragalin. Hp cht ny c mt trong
nhiu loi thc vt v c hot tnh chng xi ha mnh. Tuy nhin, y l ln u
tin hp cht TG13 c pht hin t chi Tetradium.
97

C
156,7
133,5
177,6
160,8
99,3
162,2
94,5
156,0
105,5
120,7
130,9
115,1
160,2
100,8
74,2
77,5
69,9
76,4
60,8
C
156,65
133,44
177,71
161,43
98,97
164,35
93,96
156,63
104,26
121,15
131,15
115,40
160,14
101,13
74,44
77,62
70,10
76,61
61,07
C
2
3
4
5
6
7
8
9
10
1
2,6
3,5
4
1
2
3
4
5
6
H (J = Hz)
6,20 (d, 2,0)
6,42 (d, 2,0)
8,04 (dd, 1,5, 7,0)
6,88 (dd, 1,5, 7,0)
5,45 (d, 7,5)
3,18 (m)
3,08 (m)
3,09 (m)
3,25 (m)
3,33 (m)
3,56 (dd, 5,5, 11,0)
DEPT
C
C
C
C
CH
C
CH
C
C
C
CH
CH
C
CH
CH
CH
CH
CH
CH2
HMBC (HC)
7, 5, 10, 8
7, 9, 10, 6
4, 2, 2, 6
4, 1, 3, 5
3
1, 3
4
5, 3
C ca kaempferol 3-O--D-glucopyranoside [128].
4.2.14. Hp cht TG14: Nicotiflorin
HO
OH
OH
OH
10
5
HO
6'
2
4'
1'
OH
OH
3'
HO
2"
HO
1"
3"
OH
OH
H 3C
HO
OH
6"
5'"
4'"
H 3C
HO
1'"
2'"
O
HO
HO
OH
OH
Hnh 62. Cu trc v cc tng tc HMBC chnh ca TG14.

Hp cht TG14 l mt hp cht dng tinh th hnh kim, mu vng. Hp
cht TG14 c xc nh c cu trc tng t nh hp cht TG13 bi s ging
nhau v s liu ph NMR gia hai hp cht. Tuy nhin, im khc bit l trong cc
d liu ph ca TG14 xut hin thm cc tn hiu c trng ca mt n v ng
rhamnose (Bng 21) so vi TG13 (Bng 20).
98

C
2
3
4
5
6
7
8
9
10
1
2, 6
3, 5
4
1
2
3
4
5
6
C#
158,5
135,5
179,4
163,0
100,0
166,1
94,9
159,4
105,6
122,7
132,4
116,1
161,5
104,6
75,7
78,1
71,4
77,2
68,5
C
156,89
133,27
177,42
161,23
98,79
164,26
93,80
156,55
104,00
120,94
130,90
115,14
159,92
101,40
74,22
75,78
69,98
76,42
66,93
DEPT
C
C
C
C
CH
C
CH
C
C
C
CH
CH
C
CH
CH
CH
CH
CH
CH2
1
2
3
4
5
6
102,4
72,1
72,3
73,9
69,7
17,9
100,79
70,38
70,65
71,88
68,27
17,72
CH
CH
CH
CH
CH
CH3
H (J = Hz)
6,20 (d, 2,0)
6,40 (d, 2,0)
7,98 (d, 8,5)
6,88 (d, 9,0)
5,31 (d, 7,5)
3,16 *
3,24*
3,06*
3,22 (m)
3,27*
3,69 (d 10,5)
4,38 (br s)
3,42*
3,28*
3,09*
3,27*
0,98 (d, 6,0)
HMBC (HC)
5, 7, 8, 10
6, 7, 9, 10
2, 2, 3, 4, 5, 6
1, 2, 3, 4, 5, 6
3, 3
1
2
3, 6
6
4
6 , 2, 3, 5
3, 4
2, 4
2, 3, 6
3
4, 5
C ca nicotiflorin [129], *cc tn hiu b chng lp.
Trn ph 13C-NMR (Hnh 66) v DEPT (Hnh 67) xut hin tn hiu ca 27
nguyn t cacbon, trong c 9 nguyn t cacbon bc bn, 16 nhm methine, 1
nhm methylene v 1 nhm methyl.
Thng qua cc tng tc trc tip H-C trn ph HSQC chuyn dch ha
hc ca cc proton c gn vi cc cacbon tng ng. Phn tch ph
13
C-NMR
(Hnh 66) ca TG14 thy chuyn dch ha hc ca cacbon methylen C-6 (C

66,93) ca phn ng chuyn mnh v vng trng thp so vi cacbon tng ng
ca TG13 (C 61,07), cho php d on v tr lin kt ca phn ng rhamnose ti
99
v tr C-6. D on ny c khng nh bng tng tc HMBC (Hnh 69) gia H1 (H 4,38) vi C-6 (C 66,93); ng thi phn ng c xc nh lin kt ti
C-3 ca flavonol do xut hin tng tc HMBC gia H-1 (H 5,31) v C-3 (C
133,27). Cc v tr trong phn t c xc nh chnh xc bi HSQC (Hnh 68) v
HMBC (Hnh 69).
Kt hp cc kt qu phn tch trn cng vi s so snh s liu ph NMR ca
TG14 vi s liu ph ca hp cht nicotiflorin [129] thy hon ton ph hp. T
, hp cht TG14 c xc nh l nicotiflorin, mt flavonoid ln u c phn
lp t chi Tetradium.
100
Hnh 64. Ph gin 1H-NMR ca TG14 (a).
Hnh 65. Ph gin 1H-NMR ca TG14 (b)

101

102

103
4.2.15. Hp cht TG15: Trifoline

OH
OH
4'
1'
HO
9
HO
6'
OH
OH
OH
OH
10
5
HO
1''
OHO
3"
6"
OH
OH
OH
OH

Hp cht TG15 thu c di dng tinh th hnh kim, mu vng. Trn ph
ESI-MS ca TG15 xut hin pic ion ti m/z 471 [M+Na]+ ph hp vi cng thc
phn t C21H20O11.
Trn ph 1H-NMR (Ph lc 7) ca TG15 xut hin cp tn hiu doublet ti
ti H 6,19 (d, J = 1,5 Hz) v 6,42 (d, J = 1,5 Hz) in hnh cho hai proton v tr
C-6 v C-8 ca vng A ca hp cht flavonol. Cp hai tn hiu doublet khc ti H
6,85 (d, J = 8,5 Hz) v 8,06 (d, J = 8,5 Hz) c trng cho vng thm B th para.
Tn hiu proton anome ti H 5,37 (d, J = 7,5 Hz) gi trong TG15 c mt 1 phn
ng.
Ph 13C-NMR ca TG15 xut hin tn hiu ca 21 nguyn t cacbon, trong
c 8 nguyn t cacbon bc bn, 11 nhm methine v 1 nhm methylene. Trong
c 6 tn hiu cacbon ti C 101,81 (C-1), 71,27 (C-2), 73,18 (C-3), 67,94 (C4), 75,80 (C-5), 60,24 (C-6) c trng cho s c mt ca mt phn t ng. So
snh s liu ph ca TG15 vi s liu ph ca TG13 cho thy c s ging nhau c
bn ngoi tr s liu ca phn ng, chng t y khng phi l ng glucose.
Kt hp tra cu ti liu tham kho v phn tch ph 1H-NMR ca TG15 thy tn
hiu H-4 ti H 3,66 (t) c J = 2,5 Hz v hng s tng tc gia H-3, H-4 (JH-3-H4=
2,5) thp cho php xc nh nhm hydroxyl c cu hnh axial, chng t phn
ng ca hp cht TG15 l galactose. Cu trc ca hp cht TG15 cn c

khng nh thm bng cc ph NMR hai chiu HSQC v HMBC. Kt hp vi cc
gi tr ph NMR c phn tch thy TG15 hon ton ph hp vi cc gi tr
tng ng ca hp cht kaempferol 3-O--D-galactopyranoside. [130]. T c
th kt lun hp cht TG15 l kaempferol 3-O--D-galactopyranoside (trifoline),
y l ln u tin phn lp c t chi Tetradium.
104

C
Aglycone
2
3
4
5
6
7
8
9
10
1
2, 6
3, 5
4
3-O-Gal
1
2
3
4
5
6
C#
DEPT H (J = Hz)
HMBC (HC)
156,1
133,2
177,4
161,1
98,6
164,0
93,5
156,3
103,8
120,9
130,8
114,9
159,8
156,39
133,31
177,54
161,24
98,86
164,54
93,79
156,48
103,89
120,93
131,02
115,14
160,00
C
C
C
C
CH
C
CH
C
C
C
CH
CH
C
6,19 (d, 1,5)

6,42 (d, 1,5)
8,06 (d, 8,5)
6,85 (d, 8,5)
-
5, 7, 8, 10
2, 6, 7, 10
2, 2, 4, 6
1, 2, 3, 5
-
101,7
71,2
73,1
67,8
75,8
60,2
101,81
71,27
73,18
67,94
75,80
60,24
CH
CH
CH
CH
CH
CH2
5,37 (d, 7,5)

3,53 (dd, 7,5, 9,0)
3,37 (dd, 2,5, 9,0)
3,66 (brt, 2,5)
3,34 (m)
3,28*
3,43*
3
1, 3
2
2, 3
4
5
5
C ca kaempferol 3-O--D-galactopyranoside [130].
4.2.16. Hp cht TG16: Quercetin

OH
OH
3'
4'
HO
1'
O
7
9
5
OH
10
4
OH
Hnh 71. Cu trc ha hc ca TG16.

Hp cht TG16 thu c di dng tinh th mu vng khi trin khai trn bn
sc k v hin mu bng dung dch sunforic acid 10% thy xut hin mu vng nn
d on l mt hp cht flavonoid. Ph 1H-NMR (Ph lc 8) ca hp cht TG16
105
xut hin cc tn hiu ti H 6,89 (d, J = 8,5 Hz), 7,64 (dd, J = 2,0, 8,5 Hz) v 7,74
(d, J = 2,0 Hz) gi s c hai nhm th vo vng B v tr C-3 v C-4. Trn ph
cn c hai hin tn hiu ti H 6,19 (d, J = 2,0 Hz) v 6,38 (d, J = 2,0 Hz) l du
hiu nhn bit ca mt hp cht flavonol.
Phn tch cc d kin ph NMR ca TG16 v kt hp so snh vi cc s liu
ph ca hp cht quercetin trong ti liu cng b [131] thy hon ton ph hp, t
c th kt lun hp cht TG16 l quercetin ( 3,3,4,5,7-pentahydroxyflavone) l
mt flavonoid phn lp c t nhiu loi thc vt trong thin nhin.
#
C
2
3
4
5
6
7
8
9
10
1
2
3
4
5
6
C
146,8
135,6
175,7
160,6
98,1
163,8
93,3
156,1
103,0
121,9
115,1
145,0
147,6
115,5
119,9
#
C
147,72
137,19
177,27
162,45
99,22
165,51
94,40
158,19
104,49
124,13
115,98
146,17
148,72
116,20
121,67
C ca quercetin [131].
H (J = Hz)
6,19 (d, 2,0)
6,39 (d, 2,0)
7,74 (d, 2,0)
6,89 (d, 8,5)
7,64 (dd, 2,0, 8,5)
4.2.17. Hp cht TG17: -Tocopherol

1'
HO
8a
8
4'
6
3
2'
4a
14''
4''
15''
8''
O
1''
16''
12''
13''
3'

Hp cht TG17 thu c di dng du, mu vng. Trn ph 1H-NMR
(Hnh 73) xut hin tn hiu singlet ca 4 nhm methyl bc ba ti H 2,11 (6H, s),
2,16 (3H,s) v 1,23 (3H, s) v tn hiu ca 4 nhm methyl chng chp ti H 0,85.
106

C
1
2
3
4
4a
6
7
8
8a
1
2
3
4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C#
118,5
144,5
121,0
122,6
145,5
74,5
31,5
20,8
117,4
11,8
12,2
11,3
23,8
39,8
21,0
37,5
32,7
37,3
24,8
37,4
32,8
37,4
24,5
39,4
28,0
22,6
19,7
19,8
22,7
DEPT
C
118,47
C
144,47
C
121,02
C
122,63
C
145,57
C
74,54
C
31,57
CH2
20,77
CH2
117,38
C
11,77
CH3
12,21
CH3
11,27
CH3
23,81
CH3
39,84
CH2
21,05
CH2
37,46
CH2
32,72
CH
a)
37,30
CH2
24,81
CH2
a)
37,44
CH2
32,81
CH
a)
37,44
CH2
24,45
CH2
39,39
CH2
27,99
CH
22,63
CH3
b)
19,66
CH3
b)
19,76
CH3
22,72
CH3
H (J = Hz)
2,11 (s)
2,16 (s)
2,11 (s)
1,23 (s)
0,85*
0,85*
0,85*
0,85*
C ca -tocopherol [132], a,b) Cc gi tr ny c th thay i cho nhau,*tn hiu chng chp.
Trn ph 13C-NMR (Hnh 75) v DEPT (Hnh 76) thy xut hin tn hiu ca
29 nguyn t cacbon trong c 7 cacbon bc bn, 3 cacbon methine, 11 cacbon
methylen v 8 cacbon methyl. Tn hiu ca 6 nguyn t cacbon bc bn thuc mt
vng thm b th hon ton. Kt hp so snh s liu ph NMR ca TG17 vi hp
cht -tocopherol thy hon ton ph hp tt c cc v tr [132]. Cc phn tch
trn cho php khng nh hp cht TG17 chnh l -tocopherol. Hp cht ny c
phn lp ln u tin t chi Tetradium.
107

108

109
4.2.18. Hp cht TG18: (2E,4E) N-Isobutyltetradeca-2,4-dienamide

4'
14
13
11
H
N
2'
3'
1'
H
N
O

Hp cht TG18 thu c di dng du, khng mu. Trn ph HR-ESI-MS
xut hin pic ion gi phn t ti m/z 280,2640 [M+H]+ (tnh ton l thuyt cho cng
thc C18H34NO: 280,2635) cho php xc nh cng thc phn t ca TG18 l
C18H33NO (M = 279).
Trn ph 1H-NMR (Hnh 79) xut hin tn hiu c trng ca 3 nhm methyl
ti 0,92 (6H, d, J = 7,0 Hz) v 0,86 (3H, t, J = 7,0 Hz) cng vi tn hiu ca 4
proton olefin ti H 5,75 (d, J = 15,0 Hz), 6,07 (m), 6,12 (dd, J = 10,0, 15,0 Hz) v
7,19 (dd, J = 10,0, 15,0 Hz). Trn ph 13C-NMR (Hnh 81) v DEPT (Hnh 82) ca
TG18 xut hin tn hiu ca 18 nguyn t cacbon trong c 1 cacbon bc bn, 5
nhm methine, 9 nhm methylen v 3 nhm methyl. Da vo chuyn dch ha
hc, xc nh c tn hiu c trng ca 1 nhm cacbonyl ti C 166,39 (C-1); 1
nhm methylen gn vi nguyn t nit ti C 46,93 (C-1); 2 lin kt i ti C
121,72 (C-2)/141,32 (C-3) v 128,20 (C-4)/143,23 (C-5). S c mt ca nhm
isobutyl cng c xc nhn ti C 46,93 (C-1), 28,64 (C-2) v 20,12 (C-3,C-4).
Da trn kt qu phn tch ph HSQC (Hnh 83) cc tn hiu proton c
gn vi tn hiu cacbon tng ng. S c mt ca nhm isobutyl c khng nh
da vo cc tng tc HMBC gia H-1 (H 3,17) vi C-2 (C 28,64)/C-3 (C
20,12)/C-4(C 20,12); tng tc gia H-2 (H 1,80) vi C-1 (C 46,93)/C-3 (C
20,12)/C-4 (C 20,12).
110
Bng 25. S liu ph NMR ca TG18 v hp cht tham kho.

C
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
2
3
4
C#
166,4
121,7
141,3
128,2
143,3
33,0
28,7
31,8
29,1
29,1
22,6
14,1
46,9
28,8
20,1
20,1
#
C
166,39
121,72
141,32
128,20
143,23
32,95
29,53
29,44
29,29
29,18
28,82
31,88
22,67
14,10
46,93
28,64
20,12
20,12
DEPT
C
CH
CH
CH
CH
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH2
CH
CH3
CH3
H (J=Hz)
5,75 (d, 15,0)
7,19 (dd, 10,0, 15,0)
6,12 (dd, 10,0, 15,0)
6,07 (m)
2,15 (m)
1,27 (m)
1,27 (m)
1,27 (m)
1,27 (m)
1,27 (m)
1,27 (m)
1,27 (m)
0,86 (t, 7,0)
3,17 (dd, 6,5, 6,5)
1,80 (m)
0,92 (d, 7,0)
0,92 (d, 7,0)
HMBC (HC)
1, 3, 4
1, 5
2, 3
3, 4
4, 5, 7
6, 8
11, 12, 14
11, 12
1, 2, 3, 4
1, 3, 4
1, 2, 4
1, 2, 3
C ca (2E,4E)-N-isobutyltetradeca-2,4-dienamide [133], *tn hin chng lp.
Cc tng tc HMBC gia H-2 (H 5,75)/H-3 (H 7,19) vi C-1 (C 166,39);

tng tc gia H-4 (H 6,12) vi C-2 (C 121,72)/C-3 (C 141,32) v gia H-5 (H
6,07) vi C-3 (H 141,32)/C-4 (C 128,20)/C-6 (C 32,95)/C-7 (C 29,53) gi s
c mt ca hai lin kt i ti C-2/C-3 v C-4/C-5 v 1 nhm cacbonyl ti C-1. Cu
hnh ca hai lin kt i ny u c xc nh l E da trn gi tr hng s tng
tc ln (JH-2-H-3 = JH-4-H-5 = 15,0 Hz). Nhnh isobutyl ni vi tetradecadienoyl qua
cu nit c xc nh bi tng tc HMBC (Hnh 84) gia H-1 (H 3,17) vi C-1
(C 166,39).
Da vo cc bng chng trn v so snh s liu ph ca TG18 vi Nisobutyl-2E,4E- tetradecadienamide [133] cho thy hon ton ph hp. T c th
khng nh TG18 l (2E,4E)-N-isobutyltetradeca-2,4-dienamide, hp cht ny
ln u c phn lp t chi Tetradium.
111
Hnh 78. Ph HR-ESI-MS ca TG18.

112

113

114

4.2.19. Hp cht TG19: (2E,4E)-N-Isobutyldeca-2,4-dienamide
4'
10
9
H
N
2'
1'
3'
O
H
N
O

Hp cht TG19 thu c di dng cht bt, mu trng. Trn ph 1H-NMR
(Ph lc 9) xut hin tn hiu c trng ca 3 nhm methyl ti 0,94 (6H, d, J = 7,0
Hz) v 0,93 (t, J = 7,0 Hz) cng vi tn hiu ca 4 proton olefin ti H 5,75 (d, J =
15,0 Hz), 6,07 (m), 6,12 (dd, J = 10,0, 15,0 Hz) v 7,19 (dd, J = 10,0, 15,0 Hz) v 1
nhm N-methylene ti H 3,08 (d, J = 6,5 Hz).
115

C
1
2
3
4
5
6
7
8
9
10
1
2
3
4
C#
166,7
122,1
140,7
128,4
141,3
33,0
28,6
31,4
22,5
14,0
46,9
28,8
20,1
20,1
C
DEPT
169,19 C
123,07 CH
142,12 CH
129,80 CH
143,94 CH
33,86 CH2
29,68 CH2
32,52 CH2
23,49 CH2
14,31 CH3
48,03 CH2
29,73 CH
20,49 CH3
20,49 CH3
H (J=Hz)
5,94 (d, 15,0)
7,13 (dd, 10,5, 15,0)
6,21 (dd, 10,5, 15,0)
6,11 (m)
2,19 (m)
1,46 (m)
1,35 (m)
1,35 (m)
0,93 (t, 7,0)
3,08 (d, 6,5)
1,81 (m)
0,94 (d, 7,0)
0,94 (d, 7,0)
HMBC (HC)
1, 4
1, 5
2, 3, 5, 6
3, 4, 6, 7
4, 5, 7, 8
5, 8, 9
8, 9
1, 2, 3, 4
1, 3, 4
1, 2, 4
1, 2, 3
C ca pellitorine o trong CDCl3 [134], *tn hiu b chng lp.
Trn ph 13C-NMR v DEPT (Ph lc 9) ca TG19 xut hin tn hiu ca 14

nguyn t cacbon trong c 1 cacbon bc bn, 5 nhm methine, 5 nhm methylen
v 3 nhm methyl. Phn tch s liu ph NMR ca TG19, c th khng nh hp
cht ny cng l mt amide c cu trc tng t hp cht TG18 nhng c mch
cacbon ngn hn.
Da vo ph HMBC, v tr hai lin kt i ti C-2/C-3 v C-4/C-5 c
khng nh da trn cc tng tc gia H-2 (H 5,94)/H-3 (H 7,13) vi C-1 (C
169,19); gia H-4 (H 6,21) vi C-2 (C 123,07)/C-3 (C 142,12) v gia H-5 (H
6,11) vi C-3 (C 142,12)/C-4 (C 129,80)/C-6 (C 33,86)/C-7 (C 29,68). Tng t
hp cht TG18, cu hnh ca hai lin kt i c xc nh l 2E,4E da trn hng
s tng tc ln ( J = 15,0 Hz). Nhm isobutyl lin kt vi decadienoyl qua cu nit
do xut hin tng tc HMBC gia H-1 (H 3,08) vi C-1 (C 169,19). T nhng
phn tch nu trn v so snh s liu ph ca TG19 vi (2E,4E)-N-isobutyldeca2,4-dienamide (pellitorine) phn lp t loi Asiasarum heterotropoides [134], c th
khng nh hp cht TG19 l (2E,4E)-N-isobutyldeca-2,4-dienamide, hp cht
ny ln u tin phn lp c t chi Tetradium.
116
4.2.20. Hp cht TG20: (2E,4E,8E)-N-Isobutyltetradeca-2,4,8-trienamide

4'
14
12
10
H
N
2'
1'
3'
H
N

Hp cht TG20 nhn c di dng du khng mu. Trn ph HR-ESI-MS
(Ph lc 10) xut hin pic ion gi phn t ti m/z 278,2483 [M+H]+ (tnh ton l
thuyt cho cng thc C18H32NO: 278,2484) cho php xc nh cng thc phn t
ca TG20 l C18H31NO (M = 277).
Ph 1H-NMR (Ph lc 10) ca TG20 xut hin tn hiu ca 3 nhm methyl
ti 0,88 (3H, t, J = 6,5 Hz) v 0,92 (6H, d, J = 7,0 Hz); cng vi 6 proton olefin ti
H 5,75 (dd, J = 5,5, 15,0 Hz), 6,08 (m), 6,16 (dd, J = 11,0, 15,0 Hz) 7,19 (dd, J =
5,5, 15,0 Hz), 5,33 (m) v 5,40 (m) v 1 nhm N-methylene ti H 3,16 (t, J = 6,5
Hz). Ph 13C-NMR v DEPT ca TG20 xut hin tn hiu ca 18 nguyn t cacbon,
bao gm 1 nhm cabon bc bn, 7 nhm methine, 7 nhm methylen v 3 nhm
methyl. Nhm N-isobutyl cng c xc nhn bi cc tn hiu ti C 46,9 (C-1),
28,62 (C-2), 20,09 (C-3/C-4). S liu ph NMR ca TG20 ging TG18 ngoi tr
s xut hin thm mt lin kt i ti C-8/C-9. Cc tn hiu proton c gn vi tn
hiu cacbon tng ng da trn kt qu phn tch ph HSQC.
Da vo ph HMBC, s c mt ca nhm N-isobutyl c khng nh bi
cc tng tc gia H-1 (H 3,16) v C-2 (C 28,62)/C-3/C-4 (C 20,11); gia H-2
(H 1,80) v C-1 (C 46,94)/C-3/C-4 (C 20,11).V tr ca ba lin kt i ca nhnh
tetradecatrienamide c xc nh ti C-2/C-3, C-4/C-5 v C-8/C-9 da trn tng
tc gia H-2 (H 5,75)/H-3 (H 7,19) vi C-1 (C 166,36); gia H-4 (H 6,16) vi C2 (C 122,06)/C-3 (C 141,10); gia H-5 (H 6,08) vi C-3 (C 141,10)/C-4 (C
128,55)/C-6 (C 33,03)/C-7 (C 26,53); gia H-7 (H 2,16) vi C-5 (C 142,24)/C-8
(C 128,22)/C-9 (C 130,98); gia H-8 (H 5,33) vi C-7 (C 26,53); v gia H-9 (H
5,40) vi C-7 (C 26,53)/C-10 (C 27,23).
117
C#
C
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
2
3
4
166,4
121,9
141,1
128,5
142,3
33,0
26,5
128,2
130,9
27,2
29,3
31,9
22,5
14,0
46,9
28,6
20,1
20,1
#
C
166,36
122,06
141,10
128,55
142,23
33,03
26,53
128,22
130,98
27,23
29,31
31,50
22,55
14,04
46,94
28,62
20,11
20,11
DEPT
C
CH
CH
CH
CH
CH2
CH2
CH
CH
CH2
CH2
CH2
CH2
CH3
CH2
CH
CH3
CH3
H (J=Hz)
HMBC (HC)
5,75 (dd, 5,5, 15,0)

7,19 (dd, 10,5, 15,0)
6,16 (dd, 10,5, 15,0)
6,08 (m)
2,18 (m)
2,16 (m)
5,33 (m)
5,40 (m)
2,01 (m)
1,35 (m)
1,35 (m)
1,35 (m)
0,88 (t, 6,5)
3,16 (d, 6,5)
1,80 (m)
0,92 (d, 7,0)
0,92 (d, 7,0)
1, 4
1, 5
3, 6
3, 6, 7
4, 5
5, 9
7
7
8, 9,11
9, 12
11,13
12, 13
1, 2, 3, 4
1, 3, 4
1, 2, 4
1, 2, 3
C ca (2E,4E,8E)-N-isobutyltetradeca-2,4,8-trienamide o trong CDCl3 [135]
Cu hnh ca lin kt i ti C-2/C-3 v C-4/C-5 c xc nh l E bi hng

s tng tc ln (J = 15,0 Hz). Cu hnh ca lin kt i C-8/C-9 c th xc nh
nu da trn chuyn dch ca cacbon allylic trn ph 13C-NMR. S chuyn dch
tuyn tnh ca tn hiu cacbon allylic ca ng phn Z (C < 29,0) v pha trng
mnh hn ng phn E (C > 31,0) khong 5 ppm. Vi dch chuyn ca C-7 l
26,53 ppm v C-10 l 37,23 hp cht TG20 th cu hnh ca ni i ti C-8/C-9
c xc nh l Z [136].
Phn tch cc tng tc trn ph HMBC cho php ghp nhnh isobutyl vi
nhnh tetradecatrienamide qua tng tc gia H-1 (H 3,16) vi C-1 (C 166,36).
T cc bng chng ph trn, kt hp vi tra cu ti liu tham kho, c th kt lun
hp cht TG20 c xc nh l (2E,4E,8E)-N-isobutyltetradeca-2,4,8trienamide, mt amide c phn lp ln u tin t chi Tetradium.
118
4.2.21. Hp cht TG21: Syringin

OH
OH
3'
1'
2'
HO
HO
6"
H3CO
HO
HO
O
5"
3"
H3CO
OCH3
2"
1"
OCH3
O
HO
HO
OH
OH

Hp cht TG21 thu c dng tinh th mu trng. Trn ph 1H-NMR (Ph
lc 11) ca TG21 xut hin cc tn hiu ca hai proton thm v tr meta ti H
6,76 (2H, s), hai proton olefin ti H 6,35 (d, J = 6,0, 16,0 Hz) v 6,57 (d, J = 16,0
Hz); hai nhm methoxy ti H 3,87 (6H, s); mt proton anome ti H 4,98 (d, J = 7,5
Hz) gi s c mt ca mt phn t ng. Trn ph 13C-NMR v ph DEPT ca
TG21 xut hin tn hiu ca 17 nguyn t cacbon,trong c: 4 cacbon bc bn, 9
nhm methine, 2 nhm methylene v 2 nhm methoxy. Cc tn hiu ti C 105,36
(C-1), 75,74 (C-2), 77,35 (C-3), 71,36 (C-4), 78,83 (C-5) v 62,61 (C-6)
khng nh s c mt ca ng -D-glucopyranoside.
Trn ph HMBC thy xut hin cc tng tc HMBC gia H-1 (H 6,57) vi
C-3/C-5 (C 154,34), C-4 (C 135,26), C-2 (C 130,06), C-3 (C 63,56) gi nhm
3-hydroxyallyl lin kt vi vng thm ti C-4; gia 2,6-OCH3 (H 3,88) v C-2/C-6
(C 154,34) khng nh nhm methoxy ti C-2/C-6 ca vng thm. Phn ng lin
kt vi vng thm qua cu oxi cng c xc nh bi tng tc gia H-1(H 4,89)
v C-1 (C 139,52). T cc kt qu thu c, kt hp so snh s liu ph ca TG21
vi cc s liu tng ng c cng b ca syringin [137] nhn c s ph
hp tt c cc v tr. Nh vy, hp cht TG21 c khng nh l syringin l mt
hp cht phenyl propanoid. y l ln u tin hp cht ny c phn lp t chi
Tetradium.
119

C
1
2
3
4
5
6
2,6OCH3
1
2
3
1
2
3
4
5
6
C#
135,9
154,4
105,5
135,3
105,5
154,4
57,1
C
135,92
154,34
105,51
135,26
105,51
154,34
57,04
DEPT
C
C
CH
C
CH
C
CH3
H (J = Hz)
6,77 (s)
6,77 (s)
-
131,3
130,1
63,6
105,4
75,8
77,9
71,4
78,4
62,6
131,26
130,06
63, 56
105,36
75,74
77,35
71,36
78,83
62,61
CH
CH
CH
CH
CH
CH
CH
CH
CH2
6,57 (d,16,0)
6,35 (6,0, 16,0)
4,24 (dd, 1,5, 5,5)
4,89 (d, 7,5)
3,50 (m)
3,45*
3,42*
3,24 (m)
3,69 (dd, 5,0, 12,0)
3,80 (dd, 2,5, 12,0)
HMBC (HC)
1, 2, 4, 5, 1
1, 3, 4, 6, 1
2,6
3,88 (s)
3, 5, 4, 3
4,3
1,2
1, 5
1, 3
4, 5
2, 6
4
4
C ca syringin o trong CD3OD [137], * tn hiu ph b trng lp.
4.2.22. Hp cht TG22: Saikolignannisode A

OH
OH
OH
3
H3CO
HO
HO
HO
5"
3"
8'
O
1"
OH
7'
1'
H3CO
5'
HO
3'
OH HO
HO
OH
OH
OH
OCH3
OCH3

Hp cht TG22 c dng bt mu vng nht. Cc ph NMR ca TG22 c
dng tng t nh cc ph tng ng ca TG21 vi s xut hin cc tn hiu c
trng ca mt vng thm b th 4 v tr, mt phn ng glucose, mt ni i ngoi
vng cu hnh trans, hai nhm methoxy v mt nhm oxymethylen.
120

C
1
2
3
4
5
6
7
8
9
OMe
1
2
3
4
5
6
C#
133,0
107,9
151,6
142,8
137,9
117,7
128,5
129,8
61,4
55,8
131,3
112,6
146,9
144,1
114,8
120,8
C
135,40
109,16
153,45
145,03
138,95
119,16
131,49
129,69
63,66
56,41
133,21
113,82
148,42
145,37
115,68
122,62
37,3
39,18
CH2
40,6
42,79
CH2
64,6
66,83
CH2
OMe
1
2
3
4
5
55,3
103,4
74,3
76,4
69,6
76,7
56,29
105,38
75,95
77,88
71,27
78,09
CH3
CH
CH
CH
CH
CH
60,8
62,47
CH2
DEPT
C
CH
C
C
C
CH
CH
CH
CH2
CH3
C
CH
C
C
CH
CH
H (J = Hz)
6,95 (d, 2,0)
6,93 (d, 2,0)
6,59 (d, 16,0)
6,34 (dt, 6,0, 16,0)
4,24 (dd, 1,5, 5,5)
3,85 ( s)
6,60 (d, 2,0)
6,57 (d, 2,0)
6,51 (dd, 2,0, 8,0)
2,75 (dd, 5,5, 14,0)
2,98 (dd, 9,5, 14,0)
3,98 (m)
3,79 (m)
3,70 (m)
3,72 (s)
4,7 (d, 7,5)
3,49 (m)
3,42( m)
3,40 (m)
3,16 (m)
3,69 (dd, 6,0, 12,0)
3,81 (dd, 1,0, 12,0)
HMBC (HC)
3, 4, 6, 7
2, 3, 4,7, 8, 1
1, 9, 2, 6
1, 9
7, 8
3
4,6, 7
1', 3'
2, 4, 7
1, 2, 6, 8, 9, 5
4, 5, 1, 6, 7, 9
5, 7, 8
3
4, 3
1, 3
2, 4
6
4
4, 5
C ca cht saikolignanoside A, o trong DMSO [138].
im khc bit ln nht trn cc ph NMR (Ph lc 12) ca TG22 so vi

cc ph ca TG21 l s xut hin thm cc tn hiu ca mt vng thm v th ba v
tr ti C 133,21 (C-1), 113,82 (C-2), 148,42 (C-3), 145,37 (C-4), 115,68 (C-5),
122,62 (C-6); mt nhm methylen ti C 39,18 (C-7); 1 nhm oxymethylen ti C
66,83 (C-9); v 1 nhm methine ti C 42,79 (C-8).
Thm vo , trn ph HMBC (Ph lc 12) thy xut hin cc tng tc gia
H-7 (H 2,75 v 2,98 vi C-5 (C 138,95)/C-1 (C 133,21)/C-2 (C 113,82)/C-6
121
(C 122,62)/C-8 (C 42,80)/C-9 (C 66,83) v gia H-8 (H 3,98) vi C-4 (C

145,03)/C-5 (C 138,96)/C-6 (C 119,16)/ C-1 (C 133,21)/ C-7 (C 39,18)/ C-9
(C 66,83) cho php xc nh chnh xc v tr lin kt ca vng thm th ba v tr, 2
nhm methylen v 1 nhm methine. V tr lin kt ca nhm methoxy ti C-3 c
xc nh bng tng tc HMBC gia proton ca methoxy (C 3,72) vi C-3 (C
148,42). Nh vy, cu trc phng ca TG22 c chng minh l 3-methoxy-4hydroxy-5-[(8)-3-methoxy-4-hydroxy-phenylpropylalcohol]-E-cinnamic alcohol4-O--D-glucopyranoside. Ha lp th ti v tr C-8 ca TG22 c xc nh l S
bi s ph hp hon ton v s liu ph vi cc s liu c cng b ca hp
cht saikolignanoside A [137]. T tt c cc phn tch nu, hp cht TG22 c
khng nh l saikolignanoside A, mt hp cht bezenoid ln u tin phn lp
c t chi Tetradium.
4.2.23. Hp cht TG23: Picraquassioside D
O
CH3
CH3
3
6'
HO
HO
HO
HO
HO
HO
1'
3'
OH
OH
O
OH
OH

Hp cht TG23 c phn lp di dng cht bt mu trng. Trn ph 1HNMR (Ph lc 13) xut hin tn hiu ca ba proton ti H 6,07 (t, J = 2,0 Hz), 6,20
(t, J = 2,0 Hz) v 6,22 (t, J = 2,0 Hz) c trng cho mt vng thm th ba ti meta;
ng thi trn ph thy xut hin tn hiu ca mt proton anome ti H 4,86 (d, J =
7,5 Hz) c trng cho s c mt ca phn ng -D-glucopyranoside. Ph
13
C-
NMR v DEPT ca TG23 xut hin tn hiu ca 13 nguyn t cacbon trong c 2

cacbon bc bn, 8 nhm methine, 1 nhm methylene v 1 nhm methyl.
122

1
2
3
4
5
6
1
2
3
4
5
C#
160,6
95,5
97,7
159,8
96,7
101,9
74,6
77,7
71,1
77,7
62,3
OCH3
55,7
DEPT
H (J = Hz)
C
160,84 C
95,53 CH
6,22 (t, 2,0)
162,87 C
97,78 CH
6,20 (t, 2,0)
160,70 C
96,77 CH
6,07 (t, 2,0)
102,18 CH
4,86 (d, 7,5)
74,82 CH
3,45 (s)
77,95 CH
3,47 (s)
71,34 CH
3,40 (s)
78,08 CH
3,42 (s)
3,92 (dd, 2,0, 12,0)
62,48 CH2
3,71 (dd 5,5, 12,0)
55,68 CH3
3,74 (s)
#
HMBC (H C)
1, 3, 4, 6
2, 3, 5, 6
1, 2, 4, 5
1, 5
1, 3, 4
2, 4
3, 5, 6
1, 4
4
5
3
C ca picraquassioside D [139].
Phn tch d liu ph, xc nh c tn hiu ca mt nhm methoxy ti ti

C 55,68 v 6 cacbon ti C 102,18 (C-1), C 74,82 (C-2), C 77,95 (C-3), C 71,34
(C-4), C 78,08 (C-5), C 62,48 (C-6) c trng ca mt phn t ng. T cc
phn tch trn, kt hp so snh s liu ph 1H- v 13C-NMR ca TG23 vi cc s
liu c cng b ca picraquassioside D [139] thy ph hp ti tt c cc v tr
tng ng. cho php khng nh hp cht TG23 chnh l picraquassioside D, mt
hp cht bezenoid ln u tin c phn lp c t chi Tetradium.
4.2.24. Hp cht TG24: Stigmatsterol
26
21
22
24
29
27
18
20
17
19
11
13
28
1
10
HO

123

#
C
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
C
37,21
31,62
71,81
42,29
140,72
121,71
31,87
31,87
50,08
36,48
21,07
39,64
42,29
56,83
24,34
28,92
55,90
12,03
19,38
40,50
21,05
138,32
129,22
51,21
31,87
21,20
25,40
18,95
12,25
C
37,25
31,66
71,81
42,30
140,75
121,73
31,90
31,90
50,15
36,51
21,09
39,77
42,30
56,87
24,37
28,93
56,05
11,99
19,41
40,51
21,22
138,33
129,27
51,24
31,90
21,22
25,41
19,04
12,26
DEPT
CH2
CH2
CH
CH2
C
CH
CH2
CH
CH
C
CH2
CH2
C
CH
CH2
CH2
CH
CH3
CH3
CH
CH3
CH
CH
CH
CH
CH3
CH2
CH3
CH3
H (J = Hz)
3,53 (m)
5,35 (br d, 3,5)
0,84 (s)
1,03 (s)
0,91 (d, 6,5)
5,15 (dd, 8,5, 15,0)
5,02 (dd, 8,5, 15,0)
0,84 (t, 8,5)

0,81 (d, 6,8)
0,86 (d, 9,5)
Gi tr #C ca stigmasterol o trong CDCl3 [140], *: tn hiu b chng lp.
Hp cht TG24 thu c di dng tinh th hnh kim mu trng. Trn ph

ESI-MS ca TG24 xut hin pic ion ti 395,3 [M -H2O+H]+ ph hp vi cng thc
phn t l C29H48O. Ph 1H-NMR (Ph lc 14) thy xut hin tn hiu ca 2 nhm
methyl bc ba ti H 0,84 (s), 1,03 (s); 3 nhm methyl bc hai ti H 0,91 (d, J = 6,5
Hz), 0,81 (d, J = 6,8 Hz), H 0,86 (3H, d, J = 9,5 Hz) v 1 nhm th methyl bc mt
ti H 0,84 (t, J = 8,5 Hz). Trn ph cng xc nhn s c mt ca nhm -OH (H
124
3,53, m, H-3) ti C-3. Trn ph cng xc nhn s c mt ca lin i ti H 5,32 (br

s) v mt lin kt i trans khc ti H 5,15 (dd, 8,5, 15,0)/ 5,02 (dd, 8,5, 15,0).
Ph
13
C-NMR v ph DEPT (Ph lc 14) ca TG24 xut hin 29 tn hiu
cacbon, gm c 3 cacbon bc bn, 11 nhm methine, 9 nhm methylen v 6 nhm

methyl c trng ca mt khung sterol. c bit, tn hiu ca hai cp olefin c
xc nhn ti C-5 (C 140,75)/C-6 (C 121,73) v C-22 (C 138,33)/C-23(C 129,27).
Da vo cc phn tch trn v kt hp so snh s liu ph
13
C-NMR ca
TG24 vi cc s liu c cng b ca stigmasterol [140] thy hon ton ph

hp. Nh vy, TG24 c khng nh l stigmasterol.
4.2.25. Hp cht TG25: Daucosterol
26
21
22
29
24
27
18
20
17
19
11
28
13
1
10
HO
O
HO
HO
OH
HO
O
HO
HO
OH

Hp cht TG25 thu c dng cht bt mu trng. Trn ph ESI-MS ca
TG25 xut hin pic ion ti 397,3[M -C6H12O6+H]+ ph hp vi cng thc phn t
l C35H60O6.
Ph 1H-NMR (Ph lc 15) ca TG25 cho thy s c mt ca hp cht c
khung sterol t trng bi cc tn hiu ca 2 nhm methyl bc ba ti H 0,68 (s), H
0,96 (s), 3 nhm methyl bc hai ti H 0,91 (d, J = 6,5 Hz), H 0,83 (d, J = 7,3 Hz),
H 0,81 (d, J = 6,8 Hz) v 1 nhm methyl bc mt ti H 0,84 (t, J = 7,6 Hz). Trn
ph cng xc nhn s c mt ca mt proton olefin ti H 5,32 (br s) (C-5/C-6). S
xut hin ca mt phn t ng glucosyl cng c xc nh trn ph 1H-NMR
bi tn hiu proton anome ti H 4,22 (d, J = 8,0 Hz).
125

C
Aglycon
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
3-O-Glc
1
2
3
4
5
6
C#
DEPT
37,0
31,6
78,9
39,5
141,6
121,9
31,6
31,7
50,0
36,5
20,8
38,5
42,1
56,5
24,5
28,7
55,8
12,0
19,0
36,0
18,5
34,0
28,0
45,7
28,9
19,5
22,8
18,7
12,0
36,79 CH2
29,22 CH2
76,94 CH
38,28 CH2
140,42 C
121,10 CH
31,32 CH2
31,38 CH
49,58 CH
36,16 C
20,55 CH2
39,33 CH2
41,81 C
56,14 CH
23,80 CH2
27,72 CH2
55,42 CH
11,61 CH3
18,90 CH3
35,43 CH
18,56 CH3
33,33 CH2
25,46 CH2
45,13 CH
28,70 CH2
19,63 CH3
22,58 CH
19,03 CH3
11,73 CH3
100,9
73,2
76,2
70,0
75,4
100,79
73,42
76,67
70,07
76,67
CH
CH
CH
CH
CH
61,7
61,07
CH2
H (J= Hz)
HMBC (HC)
3,43 (m)
5,32 (br s)
4, 8, 10
0,68 (s)
0,96 (s)
12, 13, 14, 17

1, 5, 9, 10
0,91 (d, 6,5)
17, 20, 22
0,84 (t, 7,6)
25
0,81 (d, 6,8)

0,83 (d, 6,8)
24, 27, 29
24, 27, 28
4,22 (d, 8,0)

2,90 (m)
3,12 (m)
3,02 (m)
3,07 (m)
3,40 (m)
3,64 (dd, 6,0, 10,0)
3
-
C ca daucosterol o trong CDCl3 [141].
Ph 13C-NMR (Ph lc 15) ca TG25 xut hin 35 tn hiu cacbon, trong

29 tn hiu c xc nh l ph thuc vo khung sterol ti v 6 tn hiu cn li c
126
trng cho mt ng glucozo ti C 100,8 (C-1), C 73,42 (C-2), 76,67 (C-3),

70,08 (C-4), 76,67 (C-5), 61,07 (C-6).
Thng qua cc tng tc trn ph HSQC (Ph lc 15), chuyn dch ha
hc ca cc cacbon c gn vi cc proton tng ng. Trn ph HMBC, tn hiu
tng tc gia proton anome 4,22 (d, J = 8,0 Hz, H-1) vi C-3 (C 76,94) cho
php xc nh v tr lin kt ca n v ng vo v tr C-3; tng tc gia proton
olefin H 5,32 vi C-4 (C 38,29)/ C-8 (31,38)/ C-10 (36,16) cho thy tn ti mt
ni i ti C5/C6.
T nhng d kin ph trn kt hp vi so snh s liu ph
C-NMR ca
13
daucosterol c cng b trong ti liu [141] thy hon ton ph hp. Nh vy,
TG25 c xc nh l daucosterol, mt hp cht kh ph bin trong cc loi thc
vt nhng y l ln u tin cng b phn lp c t chi Tetradium.
4.2.26. Hp cht TG26: 5-Hydroxymethylfurfural
O
HO
CHO
2
Hnh 92. Cu trc ha hc ca TG26

C#
152,3
123,4
110,0
161,2
177,9
57,2
C
2
3
4
5
CHO
CH2OH
#
C
153,29
124,22
110,87
163,24
179,45
57,65
H (J= Hz)
7,40 (d, 3,5)
6,60 (d, 3,5)
9,57 (s)
4,63 (s)
C ca 5-hydroxymethyl-2-furancarboxaldehyde [142]
Hp cht TG26 c phn lp dng du mu vng. Trn ph 1H-NMR

(Ph lc 16) xut hin hai tn hiu ti H 7,40 (d, J=3,5 Hz) v 6,60 (d, J=3,5 Hz) c
hng s tng tc J=3,5 Hz gi cu trc th ca vng 2,5-furan; 1 tn hiu ca
nhm cabonyl ti H 9,57 (s); v 1 nhm hydroxy methylenic (-CH2OH) ti H 4,63
127
(s). Trn ph 13C-NMR (Ph lc 16) thy xut hin tn hiu ca mt nhm cacbonyl
ti C 177,9; tn hiu ca 2 cacbon olefin ti C 123,4 (C-3), 110,9 (C-4); v 1
cacbon methylenic ti C 52,7.
Thng qua cc tng tc trn ph HSQC, chuyn dch ha hc ca cc
cacbon c gn vi cc proton tng ng. Trn ph HMBC, thy xut hin cc
tng tc gia H-3 (H 7,40)/H-4 (H 7,40) vi C-2 (C 153,29)/ C-5 (C 163,24);
tng tc gia proton ca nhm cabonyl vi C-2 (C 153,29).
So snh cc s liu ph ca TG26 vi cc gi tr ph ca 5-hydroxymethyl2-furancarboxaldehyde c cng b trong ti liu tham kho [142] thy hon
ton ph hp. Nh vy, TG26 c khng nh l 5-hydroxymethyl-2furancarboxaldehyde (5-hydroxymethylfurfural) l mt hp cht fufural c
phn lp t loi Cirsium chlorolepis, nhng y l ln u tin TG26 phn lp c
t loi T. glabrifolium.
Kt lun:
T l v v thn cy du du l nhn, s dng kt hp cc phng php sc
k phn lp c 26 hp cht, bao gm: mt glycosid ester, nm alkaloid, bn
tritrerpenoid, su flavonoid, mt dn xut methyl ca phenol, ba amide, ba
benzenoid, hai sterol v mt fufural. Trong , c mt hp cht flavonoid l
epimedoside C (TG12) phn lp c vi lng ln (c gom t tt c cc phn
on tch chit c 21,54g) t l cy du du l nhn
T hai su hp cht phn lp c c mt hp cht mi ln u tin phn
lp c t t nhin v 15 hp cht ln u tin phn lp c t chi Tetradium,
a tng s hp cht c phn lp t cy du du l nhn t 74 hp cht ln thnh
90 hp cht v cc cht phn lp t loi Tetradium t mt 135 hp cht ln thnh
151 hp cht gp phn lm r hn thnh phn ha hc ca cy du du l nhn.
Cu trc ha hc v tn gi ca 26 hp cht phn lp c t cy du du l
nhn c trnh by trong bng 34 v Hnh 93 di y:
128
OH
O
O
HO
HO
OCH3
TG4
R
TG2: H
TG3: CH3
O
TG5
OH
HO
OH
OH
TG6
TG7
TG9
TG8
OH
OH
HO
HO
O
HO
HO
HO
HO
OH
OH
OH
OH
O
OH
TG10
HO
TG1
O
N
HO
OCH3
N
H
H3CO
RO
OH
OH
COOH
OH
TG12
TG11
R1
OH
OH
HO
O
HO
H3CO
OR2
OH
R2
TG13:
Glc
TG14:
TG15:
O
OH
TG18
HO
HO
H
N
R1
TG16:
HO
TG17
TG21
H
N
OCH3
OH
Glc-6''-O-Rha
O
TG19
Gal
H
OH
TG22
H
N
OH
OCH3
TG20
OCH3
HO
HO
HO
OH
OH
HO
HO
HO HO
TG23
OH
TG24
TG25
Hnh 93. Cc hp cht c phn lp t cy du du l nhn.

129
HO
TG26
Bng 34. Thng k hp cht phn lp c t cc b phn cy du du l nhn

KH
Hp cht
Lp cht
Dng mu
Khi
lng
(mg)
TG1
TG2
TG3
TG4
TG5
TG6
TG7
TG8
TG9
TG10
TG11
TG12
TG13
TG14
TG15
TG16
Tetraglabrifolioside
6-Acetonyl-Nmethyldihydrodecarine
6-Acetonyl
dihydrochelerythrine
Decarine
Iwamide
Rutaecarpine
12-Hydroxyevodol
Rutaevine
Lupeol
Friedelan-3-one
Phellamurin
Epimedoside C
Astragalin
Nicotiflorin
Trifolin
Quercetin
TG17 -Tocopherol
TG18
TG19
TG20
TG21
TG22
TG23
TG24
TG25
TG26
N-Isobutyl-2E,4Etetradecadienamide
N-isobutyl-2E,4Edecadienamide
N-Isobutyl-2E,4E,8Etetradecatrienamide
Syringin
Saikolignannisode A
Picraquassioside D
Stigmatsterol
Daucosterol
5-Hydroxymethyl
furfural
glycosid ester
10
alkaloid
V thn
11
alkaloid
V thn
alkaloid
alkaloid
alkaloid
tritrerpenoid
tritrerpenoid
tritrerpenoid
tritrerpenoid
flavonoid
flavonoid
flavonoid
flavonoid
flavonoid
flavonoid
dn xut methyl
ca phenol
V thn
V thn
V thn
V thn
L
V thn
V thn
L
L
L
L
L
L
8
25
11
7
10
9
13
8
21540
30
20
10
10
V thn
10
amide
V thn
11
amide
V thn
13
amide
V thn
10
benzenoid
benzenoid
benzenoid
sterol
sterol
L
L
L
V thn
V thn
21
7
20
8
10
fufural
Tnh
mi
Mi
*
*
*
*
*
*
*
*
*
*
*
*
*
*
(Mi): Hp cht mi ln u phn lp t t nhin, * ln u phn lp t chi Tetradium.
130
4.3. KT QU TH HOT TNH SINH HC

4.3.1. Kt qu kim tra hot tnh gy c t bo in vitro
Hin nay, cc thuc c ngun gc t cc hp cht c hot tnh gy c t bo
vn chim phn ln trong cc thuc iu tr bnh ung th. Cc nghin cu theo
hng tm kim cc hp cht thin nhin c hot tnh gy c t bo vn ang c
tp trung nghin cu nhm pht trin cc tc nhn ho tr liu ung th mi, do c
nhiu u im. T cc nghin cu ny pht hin ra nhiu hp cht c hot tnh
tt gip nh hng nhng i tng c trin vng tip tc nghin cu [143].
Trong nghin cu ny, hot tnh gy c t bo in vitro ca cc hp cht phn
lp t cy du du l nhn c tin hnh xc nh trn su dng t bo ung th:
SW480 (ung th tuyn i trng ngi), LU-1 (ung th phi ngi), LNCaP (ung
th tin lit tuyn), KB (ung th t bo biu m), F1 (ung th mng t cung) v RD
(ung th mng tim). Kt qu c trnh by trong bng 35.
Bng 35. Kt qu xc nh hot tnh gy c t bo in vitro
Hp cht
TG1
TG2
TG3
TG5
TG10
TG11
TG12
TG13
TG15
TG17
TG18
TG19
TG20
TG21
TG22
TG23
Ellipticine
SW480
> 50
> 50
> 50
> 50
> 50
21,94
10,47
> 50
> 50
> 50
> 50
> 50
> 50
> 50
35,89
> 50
0,63
LU-1
34,57
> 50
> 50
> 50
> 50
8,85
7,73
> 50
> 50
> 50
> 50
> 50
> 50
> 50
22,12
> 50
0,77
IC50 (g/mL)
LNCaP
KB
> 50
> 50
> 50
3,55
> 50
25,70
> 50
49,80
> 50
> 50
12,49
> 50
6,69
> 50
> 50
> 50
> 50
> 50
> 50
> 50
> 50
42,74
> 50
20,60
> 50
16,63
> 50
> 50
30,32
> 50
> 50
> 50
0,83
0,77
F1
> 50
4,42
27,16
49,92
> 50
> 50
> 50
> 50
> 50
> 50
49,24
29,10
18,27
> 50
> 50
> 50
0,93
IC50>50: khng th hin hot tnh; ellipticine: cht i chng dng tnh
RD
> 50
4,54
26,23
34,66
> 50
> 50
> 50
> 50
> 50
> 50
49,34
21,66
17,96
> 50
> 50
> 50
0,81
Kt qu nghin cu cho thy, alkaloid TG2 th hin hot tnh mnh trn cc
dng t bo KB, F1 v RD vi IC50 ln lt l 3,55; 4,42 v 4,52 g/mL.
131
Hp cht TG12, mt flavonoid phn lp c khi lng ln t cy du du

l nhn th hin hot tnh gy c t bo mnh i vi ba dng t bo SW480, LU1, LNCaP vi IC50 ln lt l 10,47; 7,73 v 6,69 g/mL. Cng trn ba dng t bo
ny, hp cht TG11, TG22 th hin hot tnh gy c t bo vi gi tr IC50 trong
khong 8,85 35,89 g/mL.
Hp cht TG2, TG3, TG5, TG18-TG20 th hin hot tnh gy c trn ba
dng t bo KB, F1 v RD mc trung bnh vi gi tr IC50 trong khong 16,63
49,34 g/mL.
4.3.2. Kt qu kim tra hot tnh khng lao
Theo thng k, n thng 2 nm 2013 ca t chc Y t th gii, bnh lao l
bnh c s t vong ng th hai trn ton th gii, ch sau bnh HIV/AISD. Theo
kt qu ca D n phi hp qun l bnh lao trong bnh vin a khoa, chuyn
khoa do B Y t phi hp vi T chc Y t th gii th nc ta ng th 12 trong
s 22 nc c s bnh nhn lao cao nht v 14 trong s 27 nc c gnh nng bnh
nhn lao a khng thuc cao nht th gii. ng lo ngi hn, mi nm, nc ta pht
hin khong 100.000 nghn bnh nhn lao, con s ny duy tr trong sut 10 nm qua
v khng c xu hng gim.
Vi tc ng ngy cng tng ca bnh lao v s xut hin ca cc chng lao
khng thuc, vic tm kim cc hp cht c hot tnh khng lao mi c mt ngha
quan trng i vi sc khe cng ng.
Chnh v vy, cc hp cht phn lp c t cy du du l nhn cng c
sng lc kim tra hot tnh khng lao. Thc nghim c tin hnh trn 2 chng vi
khun lao th nghim Mycobacterium bovis v Mycobacterium smegmatis. Kt qu
thc nghim c trnh by trong bng 36.
T kt qu th nghim cho thy, ba hp cht amide ln u tin phn lp t
chi Tetradium l N-isobutyl-2E,4E-tetradecadienamide (TG18), N-isobutyl-2E,4Edecadienamide (TG19), N-isobutyl-2E,4E,8E-tetradecatrienamide (TG20) u th
hin hot tnh khng lao, trong : TG18 c ch chng lao th nghim M. bovis vi
gi tr MIC 22 g/mL; hai hp cht TG19, TG20 c ch chng lao th nghim M.
bovis vi gi tr MIC l 47 v 45 g/mL.
132
Bng 36. Hot tnh khng lao trn chng M. bovis v M. smegmatis
Hp cht
TG2
TG3
TG4
TG5
TG9
TG10
TG12
TG18
TG19
TG20
TG25
Rifampin
M. bovis
a kh
100
> 200
> 200
> 200
> 200
> 200
> 200
22
47
45
> 200
1,23
MIC (g/mL)
M. smegmatis
a kh
K kh
50
100
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
> 200
5,23
6,24
>200: khng th hin hot tnh; rifampin: cht i chng dng tnh.
Hp cht 6-acetonyl-N-methyldihydrodecarine (TG2) cng c ch hai chng

lao M. bovis v M. smegmatis vi gi tr MIC ln lt l 50 v 100 g/mL.
4.3.3. Kt qu kim tra hot tnh chng oxi ha
Cc gc t do c sinh ra v tch ly trong qu trnh sng. Ty thuc vo
nng m cc gc t do c tc ng tt hay xu n c th. nng thp,
chng tham gia vo nhiu qu trnh sinh ha c tc dng tt cho c th. Nhng
nng cao cc gc t do l nguyn nhn gy t bin DNA; bin tnh protein; oxi
ha lipid... t gy ra nhiu bnh nguy him nh: ung th; lo ha sm; suy gim
h thn kinh; cc bnh v h tim mch... Nn tc dng chng oxy ha ca mt sn
phm sinh hc c ngha bao trm ln vic cha tr v ngn nga nhiu loi bnh
khc nhau [144]. Chnh v vy, vic tm kim v sng lc cc hp cht t nhin c
hot tnh chng oxi ha vn c c bit quan tm bi gi tr ca n i vi i
sng con ngi.
Hot tnh chng oxi ha tiu dit gc t do DPPH ca cc hp cht c
trnh by trong bng 37. Cucurmin c s dng l cht i chng dng vi gi tr
EC50 l 51,08 g/mL. Kt qu cho thy cc hp cht th hin hot tnh chng oxi
ha mnh ch yu thuc v lp cht flavonoid. Phellamurin TG11 v quercetin
TG16 th hin hot tnh chng oxi ha DPPH vi gi tr EC50 ln lt l 19,41 v
133
11,56 g/mL. Cc hp cht TG12, TG13, TG14 v TG15 v -tocopherol TG17

th hin hot tnh chng oxi ha DPPH mc trung bnh vi gi tr EC50 trong
khong 45,3763,87 g/mL. Trong nghin cu ny, cc hp cht phn lp t cy
du du l nhn th hin hot tnh chng oxi ha mnh thuc lp cht flavonoid v
vitamin E (-tocopherol). Nhm cht ny c chng minh c tc dng chng
oxi ha nh kh nng trung ha gc t do hot ng trong phn t v ng thi
ngn chn cc phn t hot ng khi s ph hy t bo. Tc dng chng oxi ha t
cc cy thuc truyn thng cng nh cc loi thc vt giu flavonoid c s
dng rt lu i nh tr xanh [145]. V vy, vic pht hin ra nhiu flavonoid (6/26
hp cht), c bit l TG12 chim hm lng chnh trong cy du du l nhn
m ra hng s dng cy ny trong vic s dng to cc sn phm chc nng chng
lo ha.
Bng 37. Kt qu xc nh hot tnh chng oxi ha
Hp cht
TG1
TG11
TG12
TG13
TG14
TG15
TG16
TG17
EC50 (g/mL)
> 100
19,41
58,74
59,45
63,87
45,37
11,56
62,74
Hp cht
TG18
TG19
TG20
TG21
TG22
TG23
TG25
Curcumin*
EC50 (g/mL)
> 100
> 100
> 100
> 100
> 100
> 100
> 100
51,08
*curcumin: cht i chng dng tnh, EC50>100: khng th hin hot tnh
4.3.4. Kt qu kim tra hot tnh khng vi sinh vt kim nh

Cc hp cht phn lp c t cy du du l nhn c kim tra hot tnh
khng tm chng vi sinh vt kim nh, bao gm: ba chng vi khun gram (+):
Staphylococcus aureus, Bacillus subtillis, Lactobacillus fermentum; ba chng gram
(-) l: Salmonella enterica, Escherichia coli, Pseudomonas aeruginosa; hai chng
nm mc:
Aspergillus niger, Fusarium oxysporum v hai chng
nm men:
Candida albicans, Saccharomyces cerevisiae.

Kt qu cho thy, trong cc hp cht phn lp c t cy du du l nhn,
hai flavonoid l phellamurin (TG11) v trifoline (TG15) th hin hot tnh khng vi
sinh vt vi chng Staphylococcus aureus mc trung bnh vi gi tr IC50 ln lt
l 109,63 v 32,0 g/mL (Ph lc17). S. aureus l t cu vng gy nn nhiu bnh
134
l khc nhau nh nhim trng da, vim da, nng hn c th dn n nhim trng
cc c quan su (vim xng, vim ty xng, nhim trng huyt, vim mng no
m) hoc cc bnh do c t dn n ng c thc phm nng.
Kt lun:
Cc kt qu th nghim hot tnh sinh hc ca cc hp cht c trnh by
trong hnh sau:
O
OH
H3CO
HO
H3CO
OCH3
TG2
HO
TG3
TG5
Hot tnh c t bo
Hot tnh c t bo
IC50 (g/mL): 3,55 (KB), IC50 (g/mL): 25,70 (KB),
4,42 (F1), 4,54 (RD)
27,16 (F1), 26,23 (RD)
GlcO
OH
O
HO
OH
OGlc
OH
Hot tnh c t bo
IC50 (g/mL): 49,80 (KB),
49,92 (F1), 34,66 (RD)
OH
OH
HO
N
OCH3
OH
TG11
OGlc
OH
TG12
TG13
Hot tnh khng vi sinh vt

IC50 (S. aureus):109,63g/mL
Hot tnh c t bo
Hot tnh c t bo
IC
(g/mL):
10,47 (SW480),
IC50 (g/mL): 21,94 (SW480),
50
8,85 (LU-1), 12,49 (LNCaP) 7,73 (LU-1), 6,69 (LNCaP)
Hot tnh chng oxi ha
Hot tnh chng oxi ha
EC50 : 58,74 g/mL
EC50 :19,41 g/mL
Hot tnh chng oxi ha

EC50 : 59,45 g/mL
OH
OH
O
HO
HO
HO
OGlc-6''-O-Rha
OH
OH
OH
OH
OGla
OH
OH
TG14
TG15
TG16
Hot tnh chng oxi ha

EC50 :63,87 g/mL
Hot tnh khng vi sinh vt

IC50 (S. aureus): 32,00 g/mL
Hot tnh chng oxi ha
EC50 :45,37 g/mL
Hot tnh chng oxi ha

EC50 :11,56 g/mL
135
H
N
H
N
O
H
N
TG18
TG19
TG20
Hot tnh c t bo
Hot tnh c t bo
Hot tnh c t bo
IC50 (g/mL): 42,74 (KB), IC50 (g/mL): 20,60 (KB), IC50 (g/mL): 16,63 (KB),
49,24 (F1), 49,34 (RD)
29,10 (F1), 21,66 (RD)
18,27 (F1), 17,96 (RD)
Hot tnh khng lao
Hot tnh khng lao
Hot tnh khng lao
MIC (M. bovis): 22 g/mL
MIC (M. bovis): 47 g/mL MIC (M. bovis): 45 g/mL
OH
TG22
Hot tnh c t bo
IC50 (g/mL): 35,89 (SW480),
22,12 (LU-1), 30,32 (LNCaP)
OH
H3CO
HO
HO
HO
OH
OH
OCH3
Hnh 94. Kt qu th hot tnh ca cc hp cht phn lp t cy du du l nhn.

T kt qu thc nghim hot tnh nhn thy: cc hp cht phn lp c t
cy du du l nhn th hin cc hot tnh: gy c t bo, hot tnh khng lao, hot
tnh chng oxi ha v hot tnh khng vi sinh vt kim nh cc mc khc
nhau.
Trong ng ch l hp cht 6-acetonyl-N-methyldihydrodecarine (TG2)
c hot tnh mnh nht trn dng t bo KB, F1 v RD vi IC50 ln lt l 3,55;
4,42 v 4,52 g/mL.
Hp cht TG12, mt flavonoid phn lp c lng ln t cy du du l
nhn th hin hot tnh gy c t bo mnh i vi ba dng t bo SW480, LU-1,
LNCaP vi IC50 ln lt l 10,47; 7,73 v 6,69 g/mL.
Hp cht TG11, TG16 th hin hot tnh chng oxi ha mnh gi tr c ch
c hiu qu cc gc t do DPPH t EC50 ln lt l 19,41 v 11,56 g/mL
Ba hp cht amide ba hp cht amide ln u tin phn lp t chi Tetradium l
N-isobutyl-2E,4E-tetradecadienamide (TG18), N-isobutyl-2E,4E-decadienamide
(TG19), N-isobutyl-2E,4E,8E-tetradecatrienamide (TG20) u th hin hot tnh
khng lao yu.
136
KT LUN
1. T v thn v l cy du du l nhn (Tetradium glabrifolium) phn lp
v xc nh c cu trc ha hc mt hp cht mi glycoside ester:
tetraglabrifolioside (TG1) cng 25 hp cht bit bao gm: nm alkaloid: 6acetonyl-N-methyl-dihydrodecarine (TG2), 6-acetonyldihydrochelerythrine (TG3),
decarine (TG4), iwamide (TG5) v rutaecarpine (TG6); bn tritrerpenoid: 12hydroxyevodol (TG7), rutaevine (TG8), lupeol (TG9) v friedelan-3-one (TG10);
su flavonoid: phellamurin (TG11), epimedoside C (TG12), astragalin (TG13),
nicotiflorin (TG14), trifolin (TG15) v quercetin (TG16);
mt dn xut ca
phenol: -tocopherol (TG17); ba amide: N-isobutyl-2E,4E-tetradecadienamide

(TG18),
N-isobutyl-2E,4E-decadienamide(TG19)
N-isobutyl-2E,4E,8E-
tetradecatrienamide (TG20); ba benzenoid: syringin (TG21), saikolignannisode A

(TG22) v picraquassioside D (TG23); hai sterol: stigmatsterol (TG24) v
daucosterol (TG25); mt fufural: 5-hydroxymethylfurfural (TG26). Trong , c 15
hp cht ln u phn lp chi Tetradium.
2. th cc hot tnh: gy c t bo ung th in vitro, khng lao, chng oxi
ha v khng vi sinh vt kim nh ca cc hp cht phn lp c t cy du du l
nhn, kt qu th hot tnh cho thy:
- Hp cht TG2 th hin hot tnh gy c t bo mnh trn cc dng t bo
ung th, KB, F1 v RD vi cc gi tr IC50 ln lt l: 3,55; 4,42 v 4,54 g/mL;
TG12 th hin hot tnh gy c t bo mnh trn dng t bo ung th SW480, LU1, LNCaP vi IC50 ln lt l 10,47; 7,73 v 6,69 g/mL.
- Hp cht N-isobutyl-2E,4E-tetradecadienamide (TG18) th hin hot tnh
khng vi khun lao Mycobacterium bovis vi gi tr MIC 22 g/mL.
- Hp cht TG11 v TG16 th hin hot tnh tiu dit gc t do DPPH vi
gi tr EC50 ln lt l 19,41 v 11,56 g/mL.
- Hp cht TG11 th hin hot tnh khng vi khun Staphylococcus aureus
vi gi tr IC50 l 32,0 g/mL.
137
KIN NGH
T cc kt qu nghin cu v thnh phn ha hc ca cy du du l nhn, chng
ti nhn thy loi ny c s tng ng v cc thnh phn ha hc vi loi T.
ruticarpum, mt v thuc ng y c s dng t lu i Trung Quc. Tuy nhin
hin nay cy du du l nhn vn cha c ng dng v khai thc nhiu. V vy, cn
thm cc nghin cu sinh hc v dc hc khng nh thm gi tr khoa hc ca cy
du du l nhn, gp phn trong vic to ra cc sn phm phc v chm sc sc khe
cng ng.
138
CC CNG TRNH CNG B LIN QUAN N LUN N

1. Trng Th Thu Hin, Nguyn Vn Thanh, Chu Vn Minh, Phan Vn Kim,
Nguyn Vn Tuyn, an Thy Hng, Ninh Khc Bn, Nguyn Xun Cng,
Cc hp cht flavonoid glycosit phn lp t cy Tetradium glabrifolium, Tp
ch Ha hc, 2011, 49(6), 733-738.
2. Trng Th Thu Hin, Hong L Tun Anh, Phm Hi Yn, an Th Thy
Hng, Nguyn Th Cc, Dng Th Hi Yn, Dng Th Dung, Nguyn
Xun Nhim, Nguyn Anh Hng, Nguyn Vn Tuyn, Phan Vn Kim, Cc
hp cht limonoid v triterpenoit phn lp t l cy du du l nhn
(Tetradium glabrifolium), Tp ch Ha hc, 2013, 51(1), 96-102.
3. Trng Th Thu Hin, Hong L Tun Anh, Phm Hi Yn, an Th Thy
Hng, Nguyn Th Cc, Dng Th Hi Yn, Dng Th Dung, V Mnh H,
Nguyn Xun Nhim, Nguyn Vn Tuyn, Phan Vn Kim, Cc hp cht
amit v -tocopherol phn lp t v cy du du l nhn (Tetradium
glabrifolium), Tp ch Ha hc, 2013, 51(1), 127-131.
4. Truong Thi Thu Hien, Hoang Le Tuan Anh, Pham Hai Yen, Dan Thi Thuy
Hang, Nguyen Thi Cuc, Duong Thi Hai Yen, Duong Thi Dung, Vu Manh Ha,
Nguyen Xuan Nhiem, Nguyen Van Tuyen, Phan Van Kiem, Alcaloids from
the stem bark of Tetradium glabrifolium, Journal of Chemistry (Vietnamese),
2013, 51(2), 156-161.
5. Nguyn Vn Thanh, Trng Th Thu Hin, Chu Vn Minh, Phan Vn Kim,
Nguyn Vn Tuyn, an Thy Hng, Ninh Khc Bn, Tetraglabrifolioside,
mt dn xut mi ca acid glutaric phn lp t l cy Tetradium glabrifolium
(Benth.) Hartl., Tp ch Dc hc, 2013, 477(53), 43-48.
139
TI LIU THAM KHO
1. http://en.wikipedia.org/wiki/Rutaceae.
2. http://www.theplantlist.org/browse/A/Rutaceae/Tetradium/
3. Tohru, S., Toshio, M., Masanori, K., Akira, U., Limonoids and quinolone
alkaloids from Evodia rutaecarpa. Bentham. Chem. Pharm. Bull., 1988, 36,
4453-4461.
4. Abdul, Q., Paul, P. B., Alexander, I., Thomas G. H., Hu Y., Peter, G. W.,
Alkaloids and limonoids of Tetradium trichotomum: Chemotaxonomic
significance. Biochem. Sys. and Ecol., 1990, 18, 251-252.
5. Miyake, M., Maeda, H., Ifuku,Y. Bennett, R. D., Hasegawa, S., Limonoid
glucosides in Tetradium rutaecarpa. Phytochemistry, 1991, 30, 2365-2367.
6. Bi Kim Anh, Trn Vn Sung, Nguyn Mnh Cng, Dng Anh Tun, Ba
hp cht indolopyridoquinazonin ancaloit t cy T ch ba (Tetradium
Trichotomum Lour.) ca Vit Nam. Tp ch Ha hc, 2002, 40, 72-75.
7. Stevenson, P. C., Simmonds, M. S. J., Yule, M. A., Veitch, N. C., Kite, G. C.,
Irwin, D., Insect antifeedant furanocoumarins from Tetradium daniellii.
Phytochemistry, 2003, 63, 41-46.
8. Komala, I., Mawardi, R., Lian,E. C., Hazar. B. M. L., Mohd A. Sukari.,
Asmah, R., Chemical constituents of Tetradium sambucinum (Bl.) Hartley.
Malaysian J. Sci., 2006, 25, 81-86.
9. Han, X., Hong, S., Lee, D., Lee, J., Lee, M., Moon, D.-C., Han, K., Oh, K.W., Lee, M., Ro, J., and Hwang, B., Quinolone alkaloids from Evodiae
fructus and their inhibitory effects on monoamine oxidase. Arch. Pharm.
Res., 2007, 30, 397-401.
10. Wang, T. Y., Wu, J. B., Hwang, T. L., Kuo, Y. H., and Chen, J. J., A new
quinolone and other constituents from the fruits of Tetradium ruticarpum:
effects on neutrophil pro-inflammatory responses. Chem. Biodiversity, 2010,
140
7, 18281834.
11. Huang, X., Li, W., Yang, X W., New cytotoxic quinolone alkaloids from
fruits of Evodia rutaecarpa, Fitoterapia, 2012, 83, 709714.
12. Wang, X. X., Zan, K., Shi, S. P., Zeng, K. W., Jiang, Y., Guan, Y., Xiao, C.
L., Gao, H. Y., Wu, L. J., and Tu, P. F., Quinolone alkaloids with
antibacterial and cytotoxic activities from the fruits of Evodia rutaecarpa.
Fitoterapia, 2013, 89, 17.
13. Bagge,
D.,
Available
at:
http://www.colostate.edu/Depts/Entomology
/courses/en570/papers_1998/bagge.htm, Accessed on15/04/2005.

14. Maier, V. P., Bennett, R. D., Hasegwa, S., Limonin and other limonoids,. In
S. Nagy, P.E. Shaw and M.K. Veldius. Citrus Science and Technology, The
AVI Publishing Company, Inc.USA, 1977, 1, 355-396.
15. Nakagawa, H., Duan, H., Takaishi, Y., Limonoids from Citrus sudachi.,
Chem. Pharm. Bull., 2001, 49, 649-651.
16. Manners G. D., Jacob R. A., Breksa I.A. P., Hasegawa S., Schoch T. K.,
Bioavailability of citrus limonoids in humans. J. Agric. Food Chem., 2003,
51, 4156-4161.
17. Tanaka, T., Maeda, M., Kohno, H., Murakami, M., Kagami, S., Miyake, M.,
and Wada, K., Inhibition of azoxymethane-induced colon carcinogenesis in
male F344 rats by the citrus limonoids obacunone and limonin.
Carcinogenesis, 2001, 22, 193-198.
18. Bayazit, V., Konar, V., Biochemical and physiological evaluations of
limonoid as potential cancer destroyers. Journal of Animal and
Veterinary Advances, 2010, 9, 1099-1107.
19. Lam, L. K., andHasegawa, S., Inhibition of benzo[a]pyrene-induced
forestomach neoplasia in mice by citrus limonoids. Nutr. Cancer, 1989, 12,
43-47.
20. Hasegawa, S., Ou, P., Fong, C. H., Herman, C., Coggings, W . , Atkin,
141
D. R.,
Changesin limonoate A-ring lactone and limonin 17--D
glucopyranoside content of navel oranges
during fruit
growth and
maturation. J. Agric. Food Chem., 1989, 39, 262-265.

21. Miller, E. G., Fanous, R., Rivera-Hidalgo, F., Binnie, W. H., Hasegawa,
S., and Lam, L. K., The effect of citrus limonoids on hamster buccal
pouch carcinogenesis. Carcinogenesis, 1989, 10, 1535-1537.
22. Miller, E. G., Gonzales-Sanders, A. P., Couvillon, A. M., Wright, J. M.,
Hasegawa, S., and Lam, L. K., Inhibition of hamster buccal pouch
carcinogenesis by limonin 17--D-glucopyranoside. Natr. Cancer, 1992,
17, 1-7.
23. Jacob, R., Hasegawa, S., Manners, G., The potential of citrus limonoids
as anticancer agents. Perishables Handl. 2000, 8, 6-8.
24. Yang, J., Cai, X., Lu, W., Hu, C., Xu, X., Yu, Q., and Cao, P., Evodiamine
inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in
hepatocellular carcinoma cells Original. Cancer Lett., 2013, 328, 243-251.
25. Yang, L.-M., Chen, C.-F., and Lee, K.-H., Synthesis of rutaecarpine and
cytotoxic analogues Bioorg. Med. Chem. Lett., 1995, 5, 465-468.
26. Baruah, B., Dasu, K., Vaitilingam, B., Mamnoor, P., Venkata, P. P.,
Rajagopal, S., and Yeleswarapu, K. R., Synthesis and cytotoxic activity of
novel quinazolino--carboline-5-one derivatives. Bioorg. Med. Chem. 2004,
12, 1991-1994
27. Chiou, W. F., Liao, J. F., and Chen, C. F., Comparative study of the
vasodilatory effects of three quinazoline alkaloids isolated from Evodia
rutaecarpa. J. Nat. Prod., 1996, 59, 374-378.
28. Wang, G. J., Shan, J., Pang, P. K., Yang, M. C., Chou, C. J., and Chen, C. F.,
The vasorelaxing action of rutaecarpine: Direct paradoxical effects of
intracellular calcium concentration of vascular smooth muscle and
endothelial cells. J. Pharmacol. Exp. Ther., 1996, 276, 1016-1021.
142
29. Wang, G. J., Wu, X. C., Chen, C. F., Lin, L. C., Huang, Y. T., Shan, J., Pang,
P. K. T., Vasorelaxing action of rutaecarpine: Effects of rutaecarpine on
calcium channel activities in vascular endothelial and smooth muscle
cells. J Pharmacol. Exp. Ther., 1999, 289,1237-1244.
30. Yi, H. H., Rang, W. Q., Deng, P. Y., Hu, C. P., Liu, G. Z., Tan, G. S., Xu, K.
P., and Li, Y. J., Protective effects of rutaecarpine in cardiac anaphylactic
injury is mediated by CGRP. Planta Med., 2004, 70(12), 1135-1139.
31. Yu, J., Tan, G. S., Deng, P. Y., Xu, K. P., Hu, C. P., Li, Y. J., Involvement of
CGRP in the inhibitory effect of rutaecarpine on vasoconstriction induced by
anaphylaxis in guinea pig. Regul Pept, 2005, 125(1-3), 93-97.
32. Chiou, W. F., Shum, A. Y., Liao, J. F., Chen, C. F., Studies of the cellular
mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive
component extracted from an herbal drug. J. Cardiovasc. Pharmacol., 1997,
29, 490-508.
33. Deng, P.Y., Ye, F., Cai, W. J., Tan, G. S., Hu, C. P., Deng, H. W., Li, Y. J.,
Stimulation of calcitonin gene-related peptide synthesis and release:
mechanisms for a novel antihypertensive drug, rutaecarpine. J. Hypertens.
2004, 22,1819-1829.
34. Qin, X. P., Zeng, S. Y., Li, D., Chen, Q. Q., Luo, D., Zhang, Z., Hu, G. Y.,
Deng, H. W., and Li, Y. J., Calcitonin gene related peptide-mediated
depressor effect and inhibiting vascular hypertrophy of rutaecarpine in
renovascular hypertensive rats. J. Cardiovasc. Pharmaco.l, 2007, 50, 654659.
35. Hu, C. P., Xiao, L., Deng, H. W., Li, Y. J., The cardioprotection of
rutaecarpine is mediated by endogenous calcitonin release-gene peptide
through activation of vanilloid receptors in guinea-pig hearts. Planta Med,
2002, 68, 705-709.
36. Li, D., Zhang, X. L., Chen, L., Yang, Z., Deng, H. W., Peng, L., Li, Y.J.,
Calcitonin gene- related peptide mediates the cardioprotective effects of
143
rutaecarpine against
ischaemia-perfusion
injury
in
spontaneously
hypertensive rats. Clin. Exp. Pharmacol. Physiol., 2009, 36, 662-667.

37. Qin, X. P., Zeng, S. Y., Li, D., Chen, Q. Q., Luo, D., Zhang, Z., Hu, G. Y.,
Deng, H. W., and Li, Y. J., Calcitonin
gene-related
peptide-mediated
depressor effect and inhibiting vascular hypertrophy of rutaecarpine in

renovascular hypertensive rats. J Cardiovasc Pharmacol, 2007, 50(6), 654659.
38. Li, D., Peng, J., Xin, H. Y., Luo, D., Zhang, Y. S., Zhou, Z., Jiang, D. J.,
Deng, H. W., and Li, Y. J., Calcitonin
antihypertensive
and
gene-related
anti- platelet effects
by
peptide-mediated
rutaecarpine
in
spontaneously hypertensive rats. Peptides, 2008, 29,1781-1788.

39. Sheu, J. R., Hung, W. C., Lee, Y. M., Yen, M. H., Mechanism of inhibition
of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodiae
rutaecarpa. Eur. J. of Pharmacol., 1996, 318, 469-475.
40. Sheu, J. R., Pharmacological effects of Rutaecarpine, an alkaloid isolated
from Evodia rutaecarpa. Cardiovasc. Drug Rev. 1999, 17, 237-245.
41. Sheu, J. R., Hung, W. C., Wu, C. H., Lee, Y. M., and Yen, M. H.,
Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia
rutaecarpa, on platelet plug formation in in vivo experiments. Br. J.
Haematol., 2000, 110, 110-115.
42. Rang, W. Q., Du, Y. H., Hu, C. P., Ye, F., Xu, K. P., Peng, J., Deng, H. W.,
Li, Y. J., Protective effects of evodiamine on myocardial ischemiareperfusion injury in rats. Planta Med., 2004, 70, 1140-1143.
43. Chiou, W. F., Chen, C. F., Pharmacological profile of evodiamine in isolated
rabbit corpus cavernosum. Eur. J. Pharmacol., 2002, 446,151-159.
44. Chiou, W. F., Liao, J. F., Shum, A. Y., Chen, C. F., Mechanisms of
vasorelaxant
effect
of
dehydroevodiamine:
bioactive
isoquinazolinocarboline alkaloid of plant origin. J. Cardiovasc. Pharmacol.,

1996, 27, 845-853.
144
45. Yuan, S. F., General research on Evodia rutaecarpa Juss. Benth. Lishizhen
Med Mater Med Res, 2000, 11, 281-282.
46. Lee, H. S., Oh, W. K., Choi, H. C., Lee, J. W., Kang, D. O., Park, C. S.,
Mheen, T.-I., and Ahn, J. S., Inhibition of Angiotensin II Receptor Bindingby
Quinolone Alkaloids from Evodia rutaecarpa. Phytother. Res., 1998, 12,
212214.
47. Yamahara, J., Yamada, T., Kitani, T., Naitoh, Y., Fujmura, H., Antianoxic
action and active constituents of Evodia Fructus. Chem. Pharm. Bull., 1989,
37, 1820-1822.
48. Yamahara, J., Yamada, T., Kitani, T., Naitoh, Y., Fujimura, H., Antianoxic
action of evodiamine, an alkaloid in Evodia rutaecarpa fruit. J.
Ethnopharmacol., 1989, 27, 185-192.
49. Kim, S. T., Kim, J. D., Lyu, Y. S., Lee, M. Y., Kang, H. W., Neuroprotective
effect of some plant extracts in cultured CT105-induced PC12 cells. Biol.
Pharm. Bul., 2006, 29, 2021-2024.
50. Park, C. H., Kim, S. H., Choi, W., Lee, Y. J., Kim, J. S., Kang, S. S., Suh Y.
H., Novel anticholinesterase
and
antiamnesic
activities
of
dehydro-
evodiamine, a constituent of Evodia rutaecarpa. Planta Med., 1996, 62,

405-409.
51. Decker, M., Novel inhibitors of acetyl- and butyrylcholinesterase derived
from the alkaloids dehydroevodiamine and rutaecarpine. Eur. J. Med. Chem.,
2005, 40, 305-313.
52. Park, E. J., Suh, Y. H., Kim, J. Y., Choi, S., and Lee, C. J., Long-lasting
facilitation by dehydroevodiamine. HCl of synaptic responses evoked in the
CA1 region of rat hippocampal slices. Neuroreport, 2003, 14, 399-403.
53. Lim, D. K., Lee, Y. B., Kim, H. S., Effects of dehydroevodiamine exposure
on glutamate release and uptake in the cultured cerebellar cells. Neurochem.
Res., 2004, 29, 407-411.
145
54. Angus, D. C., Epidemiology of severe sepsis in the United States: Analysis of
incidence, outcome, and associated costs of care. Crit. Care Med., 2001, 29,
1303-1310.
55. Liu, Y. N., Pan, S. L., Liao, C. H., Huang, D. Y., Guh, J. H., Peng, C. Y.,
Chang, Y. L., Teng, C. M., Evodiamine
inflammatory
represses
hypoxia-induced
proteins expression and hypoxia-inducible factor 1 alpha
accumulation in RAW 264.7. Shock, 2009, 32, 263-269.

56. Moon, T. C., Murakami, M., Kudo, I., Son, K. H., Kim, H. P., Kang, S. S.,
Chang, H. W., A new class of COX-2 inhibitor, rutaecarpine from
Evodia rutaecarpa. Inflamm. Res., 1999, 48(12), 621-625.
57. Hung, P. H., Lin, L. C., Wang, G. J., Chen, C. F., Wang, P. S., Inhibitory
Effect of Evodiamine on aldosterone release by zona glomerulosa cells in
Male Rats, Chin. J. Physiol., 2001, 44(2), 53-57.
58. Peng, L., Li, Y.J., The vanilloid receptor TRPV-1: Role in cardiovascular and
gastrointestinal protection, Eur. J. Pharmacol., 2010, 627, 1-7.
59. Kobayashi, Y., The nociceptive and anti-nociceptive effects of evodiamine
from fruits of Evodia rutaecarpa in mice, Planta Med., 2003, 69, 425-428.
60. Pearce, L. V., Petukhov, P. A., Szabo, T., Kedei, N., Bizik, F., Kozikowski,
A. P., Blumberg, P. M., Evodiamine functions as an agonist for the
vanilloid receptor TRPVI. Org. Biomol. Chem., 2004, 2, 2281-2286.
61. Kobayashi, Y., Hoshikuma, K., Nakano, Y., Yokoo, Y., Kamiya, T., The
positive inotropic
and
chronotropic
effects
of
evodiamine
and
rutaecarpine, indoloquinazoline alkaloids isolated from the fruits of Evodia

rutaecarpa, on the guinea-pig isolated right atria: Possible involvement
of vanilloid receptors. Planta Med., 2001, 67, 244-248.
62. Wang, L., Hu, C. P., Deng, P. Y., Shen, S. S., Zhu, H. Q., Ding, J. S., Tan, G.
S., Li, Y. J., The protective effects of rutaecarpine on gastric mucosa injury in
rats, Planta Med, 2005, 71, 416-419.
146
63. Liu, Y. Z., Zhou, Y., Li, D., Wang, L., Hu, G. Y., Peng, J., Li, Y. J.,
Reduction of asymmetric dimethylarginine in the protective effects of
rutaecarpine on gastric mucosal injury. Can. J. Physiol. Pharmacol., 2008,
86, 675-681.
64. Matsuda, H., Yoshikawa, M., Linuma, M., Kobo, M., Antinociceptive and
anti-inflammatory activities of limonin isolated from the fruits of
Evodia rutaecarpa var. bodinieri. Planta Med., 1998, 64, 339-342.
65. Matsuda, H., Wu, T. X., Tanaka, T., Linuma, M., Kubo, M., Antinociceptive
activities of 70% methanol extract of Evodiae fructus (fruit of Evodia
rutaecarpa var. bodinieri ) and its alkaloidal components, Biol. Pharm. Bull.,
1997, 20, 243-248.
66. Wang, Y., Lei, F., Wang, S., Hu, J., Zhan, H., Xing, D., Du, L., Regulatory
effects of Wuzhuyutang (Evodia prescription) and its consisting herbs on
TPH2 promoter. Zhongguo Zhong Yao Za Zhi, 2009, 34, 2261-2264.
67. Koneni, V. S., Jammikuntla, N. R., Ethika, T., Rakesh, S., Ram, R., Siron M.
R., Rare dipeptide and urea derivatives from roots of Moringa oleifera as
potential anti-inflammatory and antinociceptive agents, Eur. J. Med. Chem.,
2009, 44, 432-436.
68. Grousson, J., Pascal, P., Virginie, C., Viviane, B., Frdric, D., IFSCC
Congress 2012: 27th IFSCC Congress South Africa 2012: A new tetradium
ruticarpum extract enhances skin radiance, GATTEFOSS Research Centre,
36 Chemin de Genas, F-69804, Saint-Priest Cedex, France.
69. Ho, J. N., Lee, Y. H., Lee, Y. D., Jun, W. J., Kim, H. K., Hong, B. S., Shin,
D. H., Cho, H. Y., Inhibitory effect of aucubin isolated from Eucommia
ulmoides against UVB-induced matrix metalloproteinase-1 production in
human skin fibroblasts. Biosci. Biotechnol. Biochem., 2005, 69, 2227-2231.
70. Yarosh, D. B., Galvin, J. W., Nay, S. L., Pena, A. V., Canning, M. T., Broen,
D. A., Antiinflammatory activity in skin by biomimetic of Evodia rutaecarpa
extract from traditional Chinese medicine. J. Dermatol. Sci., 2006, 42, 13-21.
147
71. Beak, S. M., Paek, S. H., Jahng Y., Lee, Y. S., Kim, J. A., Inhibition of UVA
irradiationmodulated
signaling
pathways
by
rutaecarpine,
quinazolinocarboline alkaloid, in human keratinocytes. Eur. J. Pharmacol.,

2004, 49, 19-25.
72. Shin, Y. W., Bae, E. A., Cai, X. F., Lee, J. J., Kim, D. H., In vitro and in vivo
antiallergic effects on the fruits of Evodia rutaecarpa and its constituents.
Biol. Pharm. Bull., 2007, 30, 197-199.
73. Kano, Y., Zong, Q. N., Komatsu, K., Pharmacological properties of galenical
preparation, XIV. Body temperature retaining effect of the Chinese
traditional medicine, goshuyu-to and component crude drugs. Chem.
Pharm. Bull., 1991, 39, 690-692.
74. Tsai, T. H., Lee, T. F., Chen, C. F., Wang, L. C., Thermoregulatory effects of
alkaloids isolated from Wu-Chu-Yu in afebrile and febrile rats. Pharmacol.
Biochem. Behav., 1995, 50, 293-298.
75. Wang, T., Wang, Y., Yamashita, H., Evodiamine inhibits adipogenesis
via the EGFR-PKC alpha-ERK signaling pathway. FEBS 2009, 583, 36553659.
76. Hu, Y., Fahmy, H., Zjawiony, J. K., Davies, G. E., Inhibitory effect and
transcriptional impact of berberine and evodiamine on human white
preadipocyte differentiation. Fitoterapia, 2010, 81, 259-268.
77. Sharma, K., McCue, P., Dunn, S. R., Diabetic kidney disease in the db/db
mouse. Am. J. Physiol. Renal Physiol., 2003, 284, 11381144.
78. Shi, J., Yan, J., Lei, Q., Zhao, J., Chen, K., Yang, D., Zhaox, X., Zhang, Y.,
Intragastric administration of evodiamine suppresses NPY and AgRP gene
expression in the hypothalamus and decreases food intake in rats. Brain Res.,
2009, 1247, 71-78.
79. Kim, S. J., Lee, S. J., Lee, S., Chae, S., Han, M. D., Mar, W., Nam, K. W.,
Rutaecarpine ameliorates body weight gain through the inhibition of
148
orexigenic neuropeptides NPY and AgRP in mice. Biochem. Biophys. Res.

Commun., 2009, 389, 437-442.
80. Kobayashi, Y., Nakano, Y., Kizaki, M., Hoshikuma K., Yokoo Y., Kamiya
T., Capsaicin-like anti-obese activities of evodiamine from fruits of
Evodia rutaecarpa, a vanilloid receptor agonist. Planta Med., 2001, 67,
628-633.
81. Wang, T., Wang, Y., Kontani, Y., Kobayashi, Y., Sato, Y., Mori, N.,
Yamashita, H., Evodiamine improves diet-induced obesity in a uncoupling
proteun-1-independent manner: Involvement of antiadipogenic mechanism
and extracellularly regulated kinase/mitogen-activated protein kinase
signaling. Endocrinology, 2008, 149, 358-366.
82. Bak, E. J., Park, H. G., Kim, J. M., Kin, J. M., Yoo, Y. J., Cha, J. H.,
Inhibitory effect of evodiamine
alone
and
in
combination
with
rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related

to diabetes. Int. J. Obes., 2010, 34, 250-260.
83. Kato, A., Yasuko, H., Goto, H., Hollinshead, J., Nash, R. J., Adachi, I.,
Inhibitory effect of rhetsinine isolated from Evodia rutaecarpa on aldose
reductase activity. Phytomedicine, 2009, 16, 258-261.
84. Zhang, S., Xin, H., Li, Y., Zhang, D., Shi, J., Yang, J., Chen, X., Skimmin, a
coumarin from Hydrangea paniculata, Slows down the progression of
membranous glomerulonephritis by anti-inflammatory effects and inhibiting
immune complex deposition. Evid. Based Complement. Alternat. Med. 2013,
819296
85. Zhang, S., Yang, J., Li, H., Li, Y., Liu, Y., Zhang, D., Zhang, F., Zhou, W.,
Chen, X., Skimmin, a coumarin, suppresses the streptozotocin-induced
diabetic nephropathy in wistar rats. Eur. J. Pharmacol., 2012, 692, 78-83.
86. Ramesh, B., Viswanathan, P., Pugalendi, K. V., Protective effect of
Umbelliferone on membranous fatty acid composition in streptozotocininduced diabetic rats. Eur. J. Pharmacol., 2007, 566, 231-239.
149
87. Zheng, M. S., Zhang, Y. Z., Anti-HBsAg herbs employing ELISA technique.
Zhongguo Zhong Xi Yi Jie He Za Zhi, 1990, 10, 560-562.
88. Tominaga, K., Higuchi, K., Hamasaki, N., Hamaguchi, M., Takashima, T.,
Tanigawa, T., Watanabe, T., Fujiwara, Y., Tezuka, Y., Nagaoka, T., Kadota,
S., Ishii, E., Kobayashi, K., Arakawa, T., In vivo action of novel alkyl methyl
quinolone alkaloids against Helicobacter pylori. J Antimicrob. Chemother.,
2002, 50, 547-552.
89. ominaga, K., Higuchi, K., Hamasaki, N., Tanigawa, T., Sasaki, E., Watanabe,
T., Fujiwara, Y., Oshitani, N., Arakawa, T., Ishii, E., Tezuka, Y., Nagaoka,
T., Kadota, S., [Antibacterial activity of a Chinese herbal medicine, Gosyuyu
(Wu-Chu-Yu), against Helicobacter pylori]. Nihon rinsho. Japanese Journal
of Clinical Medicine, 2005, 63 Suppl 11, 592-599.
90. Rho, T. C., Bae, E. A., Kim, D. H., Oh, W. K., Kim, B. Y., Ahn, J. S., Lee,
H. S., Anti-helicobacterpylori activity of quinolone alkaloids from Evodiae
fructus. Biol. Pharm. Bull., 1999, 22, 1141-1143.
91. Thuille, N., Fille, M., Nagl, M., Bactericidal activity of herbal extracts. Int. J.
Hyg. Environ. Health, 2003, 206, 217-221.
92. Adams, M., Wube, A. A., Bucar, F., Bauer, R., Kunert, O., Haslinger, E.,
Quinolone alkaloids from Evodia rutaecarpa: a potent new group of
antimycobacterial compounds. Int. J. Antimicrob. Agents, 2005, 26, 262-264.
93. Kano, Y., Chen, X. F., Kanemaki, S., Zong, Q., Komatso, K.,
Pharmacokinetics of a galenic preparation. XV. Pharmacokinetics study of
evocarpine and its metabolites in rats. Chem. Pharm. Bull., 1991, 39, 3064
3066.
94. Yu, L. L., Liao, J. F., Chen, C. F., Anti-diarrheal effect of water extract of
Evodia fructus in mice. J. Ethnopharmacol., 2000, 73, 39-45.
95. Yu, X., Wu, D. Z., Protective effects of Evodia rutaecarpa, water extract on
ethanol-induced rat gastric lesions. Zhongguo Zhong Yao Za Zhi, 2006, 31,
150
1801-1803.
96. Yu, X., Wu, D. Z., Yuam, J. Y., Zhang, R. R., Hu, Z. B., Gastroprotective
effect of Fructus evodiae water extract on ethanol-induced gastric lesions in
rats, Am. J. Chin. Med. 2006, 34, 1027-1035.
97. Wu, C. L., Hung, C. R., Chang, F. Y., Lin, L. C., Pau, K. Y., Wang, P. S.,
Effects of evodiamine on gastrointestinal motility in male rats, Eur. J.
Pharmacol., 2002, 457, 169-176.
98. Zhang, T., Wang, M. W., Chen, S. W., Anti-emetic effect of ethanol extract
from Wuzhuyu broth, Zhougguo Zhong Yao Za Zhi, 2002, 27, 862-866.
99. Zhang, M., Long, Y., Sun, Y., Wang, Y., Li, Q., Wu, H., Guo, Z., Li, Y., Niu,
Y., Li, C., Liu, L., Mei, Q., Evidence for the complementary and synergistic
effects of the three-alkaloid combination regimen containing berberine,
hypaconitine and skimmianine on the ulcerative colitis rats induced by
trinitrobenzene-sulfonic acid. Eur. J. Pharmacol., 2011, 651, 187-196..
100. Vasconcelos, J. F., Teixeira, M. M., Barbosa-Filho, J. M., Agra, M. F.,
Nunes, X. P., Giulietti, A. M., Ribeiro-Dos-Santos, R., Soares, M. B., Effects
of umbelliferone in a murine model of allergic airway inflammation. Eur. J.
Pharmacol., 2009, 609, 126-131.
101. Cheng, M. J., Lee, K. H., Tsai, I. L., Chen, I. S., Two new sesquiterpenoids
and anti-HIV principles from the root bark of Zanthoxylum ailanthoides,
Bioorg. Med. Chem., 2005, 13, 59155920.
102. Cho, M. H., Shim, S. M., Lee, S. R., Mar, W., Kim, G. H., Effect of Evodiae
fructus extracts on gene expressions related with alcohol metabolism and
antioxidation in ethanol-loaded mice. Food. Chem. Toxicol., 2005, 43, 13651371.
103. Jayakumar, T. and Sheu, J.-R., Cardiovascular Pharmacological Actions of
Rutaecarpine, a Quinazolinocarboline Alkaloid Isolated From Evodia
rutaecarpa. J. Exp. Clin. Med., 2011, 3, 63-69
151
104. King, C. L., Kong, Y. C., Wong, N. S., Yeung,
H. W., Fong, H. H.,
Sankawa, U., Uterotonic effect of Evodia rutaecarpa alkaloids, J. Nat. Prod.,

1980, 43, 577582.
105. Ruberto, G., Renda, A., Tringali C., Napoli E. M., Simmonds M. S. J., Citrus
limonoids and their semi synthetic derivatives as antifeedant agents against
Spodoptera frugiperda larvae. A structure-activity relationship study. J.
Agric. Food Chem, 2002, 50, 6766-6774.
106. Kiprop, A. K., Rajab, M. S., Wanjala, F. M. E., Isolation and characterization
of larvicidal Activity components against mosquito larvae (Aedes aegypti
Linn.) from Calodendrum capense Thunb., Bull. Chem. Soc. Ethiop. 2005,
19, 145-148.
107. Si, S. H. S., Zhang, D., Thomas, G. H., Tetradium Loureiro, Fl. Cochinch.,
Flora of China, 2008, 11, 66-70.
108. Huy Bch v cng s, Cy thuc v ng vt lm thuc Vit Nam,
NXB Khoa hc v K thut, 2003, 158-160.
109. Wu, T.-S., Yeh, J.-H., Wu, P.-L., The heartwood constituents of Tetradium
glabrifolium. Phytochemistry, 1995, 40, 121-124.
110. Ng, K.M., Gray, A.I., Waterman, P.G., But, P.P.H., Kong, Y.-C., Limonoids,
alkaloids, and a coumarin from the root and stem barks of Tetradium
glabrifolium. J. Nat. Prod., 1987, 50, 11601163.
111. Wu, T.-S., Chang, F.-C., Wu, P.-L., Kuoh, C.-S., Chen, I.-S., Constituents of
leaves of Tetradium glabrifolium. J. Chinese Chem. Soc., 1995, 42, 929-934.
112. Nguyn nh Triu, Cc phng php vt l v ha l. Nh xut bn Khoa
hc v k thut: H Ni, 2005 Vol. 2.
113. Trn Vn Sung, Ph cng hng t ht nhn trong ha hu c, Tp I, Nh
xut bn i hc Quc gia H Ni, 2002.
114. Monks, A., Scudiero, D., Skehan, P., Shoemaker, R., Paull, K., Vistica, D.,
Hose, C., Langley, J., Cronise, P., Vaigro-Wolff, A., et al., Feasibility of a
152
high-flux anticancer drug screen using a diverse panel of cultured human

tumor cell lines. J. Natl Cancer Ins., 1991, 83, 757-766.
115. Collins, L., Franzblau, S. G., Microplate alamar blue assay versus BACTEC
460
system
for
high-throughput
screening
of
compounds
against
Mycobacterium tuberculosis and Mycobacterium avium. Antimicrob. Agents

Chemother., 1997, 41, 1004-1009.
116. Molyneux, P., The use of the stable free radical diphenylpicryl hydrazyl (DPPH)
for estimating antioxidant activity. J. Sci. Technol, 2004, 26, 211-219.
117. Vanden, B., Vlietinck A.J., Methols in plant Biochemistry, 1991, 6, 47-48.
118. Song, D., Chou, G.-X., Zhong, G.-Y., Wang, Z.-T., Two new
phenylpropanoid derivatives from Codonopsis tangshen Oliv. Helv. Chim.
Acta, 2008, 91, 1984-1988.
119. Kim, S. H., Park, J. H., Kim, T. B., Lee, H. H., Lee, K. Y., Kim, Y. C., Sung,
S. H., Inhibition of antigen-induced degranulation by aryl compounds
isolated from the bark of Betula platyphylla in RBL-2H3 cells. Bioorg. Med.
Chem. Lett., 2010, 20, 2824-2827.
120. Carromberth, C. F., Paulo, C. V., Virgina, C., Evandro, L. D. O., Luiz, E. S.,
Paulo, T. S., 6-Acetonyl-N-methyl-dihydrodecarine, a new alkaloid from
Zanthoxylum riedelianum. J. Braz. Chem. Soc., 2009, 20, 379-382.
121. Martinb, M.T., Rasoanaivo, L. H., Raharisololalao, A., Phenanthridine alkaloids
from Zanthoxylum madagascariense, Fitoterapia, 2005, 76, 590-593.
122. Ngoumfo, R. M., Jouda, J.-B., Mouafo, F. T., Komguem, J., Mbazoa, C. D.,
Shiao, T. C., Choudhary, M. I., Laatsch, H., Legault, J., Pichette, A., Roy, R.,
In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum
leprieurii Guill. et Perr. Bioorg. Med. Chem., 2010, 18, 3601-3605.
123. Akira, I., Takayuki, N., Hisao, U., Indolopyridoquinazoline, furoquinoline
and canthinone type alkaloids from Phellodendron amurense Callus tissues.
Phytochemistry, 1998, 48, 285-291.
153
124. Sholichin, M., Yamasaki, K., Kasai, R., Tanaka, O.,
13
C Nuclear magnetic
resonance of lupane - type triterpenes, lupeol, betulin and betuliniic acid.

Chem. Pharm. Bull., 1980, 28, 1006-1008.
125. Hisham, A., Kumar, G. J., Fujimoto, Y., Hara, N., Salacianone and
salacianol, two triterpenes from Salacia beddomei. Phytochemistry, 1995,
40, 1227-1231.
126. Miyaichi, Y., Segi, H., Tominoari, T., Studies on the constituents of the
laeves of Phellodendron japonicum Maxim, Yakugaku, Zashi, 1994, 114,
186-189.
127. Arisawa, M., Horiuchi, T., Hayashi, T., Tezuka, Y., Kikuchi, T., Morita, N.,
Studies on constituents of Evodia rutaecarpa (Rutaceae). I. Constituents of
the leaves, Chem. Pharm. Bull., 1993, 41,1472-1474.
128. Okuyama, T., Hosoyama, K., Hiraga, Y., Takemoto, T., The constituents of
Osmunda spp. II. A new flavonol glycoside of Osmunda asiatica, Chem.
Pharm. Bull., 1978, 26, 3071-3082.
129. Park, S. Y., Kim, J. S., Lee, S. Y., Bae K., Kang, S. S., Chemical constituents
of Lathyrus davidii. Nat. Prod. Sci., 2008, 14, 281-288.
130. Barbera, O., Sanz, J. F., Parareda, S., Macro, A., Furthea flavonol glycosides
from Anthyllis ononbrychioides. Phytochemistry, 1986, 25, 2361-2365.
131. Shen, C.-C., Chang, Y.-S., Hott, L.-K., Nuclear magnetic resonance studies
of 5,7-dihydroxyflavonoids. Phytochemistry, 1993, 34, 843-845.
132. Junichi, K., Kaoru, K., Masanobu, A., and Yasuko, T., Constituents of Ficus
pumila leaves. Chem. Pharm. Bull., 1998, 46, 1647-1649.
133. Stohr, J. R., Xiao, P. G., Bauer, R., Isobutylamides and a new
methylbutylamide from Piper sarmentosum. Planta Med., 1999, 65, 175-177.
134. Yasuda, I., Takeya, K., Itokawa, H., Structures of amides from Asiasarum
heterotropoides Maek. Var. Mandshuricum Maek, Chem. Pharm. Bull., 1981,
29, 564-556.
154
135. Su, R. H., Kim, M., Nakajima, S., Takahashi, S., Liu, M., Amides from the
fruits of Phellodendron chinense. J.Integra.e Plant Biol., 1994, 36, 817-820.
136. Xiong, Q., Shi, D., Yamamoto, H., and Mizuno, M. Alkylamides from
pericarps of Zanthoxylum Bungeanum. Phytochemistry, 1997, 46, 1123-1126.
137. Sugiyama, M., Nagayama, E., Kikuchi M., Lignan and phenylpropanoid
glycosides from Osmanthus asiaticus. Phytochemistry, 1993, 33, 1215-1219.
138. Li, T., Bin, W., Yuying, Z., A lignan glucoside from Bupleurum
scorzonerifolium. Chin. Chem. Lett., 2004, 15, 1053-1056.
139. Yoshikawa, K., Sugawara, S., Arihara, S., Phenylpropanoids and other
secondary
metabolites
from
fresh
fruits
of
Picrasma
quasioides.
Phytochemistry., 1995, 40, 253-256.

140. Darong, K., Juraithip, W., Wanchai, D., Biosynthesis of -sitosterol and
stigmasterol proceeds exclusively via the mevalonate pathway in cell
suspension culture of Croton stellatopilosus. Tetrahedron Lett., 2009, 49,
4067-4072.
141. Laurence, V., Catherine, L., Georges, M., Thierry, S., Hamid, A. H.,
Cytotoxic isoprenes and glycosides of long-chain fatty alcohols from
Dimocarpus fumatus. Phytochemistry, 1999, 50, 63-69.
142. Pyo, M., Jin, J., Koo, Y., Yun-Choi, H., Phenolic and furan type compounds
isolated from Gastrodia elata and their anti-platelet effects. Arch. Pharm.
Res., 2004, 27, 381-385.
143 William O.Foy, Cancer chemotherapentic Agents, Americal Chemical
Society, Washington DC., 1995.
144 Proctor P. H., Free radicals and human disease. CRC handbook of free
radicals and antioxidants, 1989, 1, 209-221.
145 Bors W., Heller W., Michel C., Saran M., Radical chemistry of flavonoits
antioxydant, Antioxydant in therapy and priventive medicine, Plemum press,
New York, 1990, 165 - 170.
155
PH LC
PH LC 1. Ph khi lng phn gii cao v ph NMR ca TG3.
Ph khi lng ca TG3.
Ph 1H-NMR ca TG3.
II
Ph 13C-NMR ca TG3.
Ph DEPT ca TG3.
III
Ph HSQC ca TG3.
Ph HMBC ca TG3.
IV
PH LC 2. Ph NMR ca TG4.
Ph 1H-NMR ca TG4.
Ph 1H-NMR gin ca TG4.

V
Ph 13C-NMR ca TG4.
Ph DEPT ca TG4.
VI
Ph HSQC ca TG4.
Ph HMBC ca TG4.
VII
Ph khi lng ca TG6.
Ph 1H-NMR ca TG6.
VIII
Ph 13C-NMR ca TG6.
IX
Ph DEPT ca TG6.
Ph HSQC ca TG6.
X
Ph HMBC ca TG6.
XI
Ph 1H-NMR ca TG9.
Ph 13C-NMR ca TG9.
XII
XIII
Ph DEPT ca TG9.
XIV
Ph 1H-NMR ca TG12.

XV
Ph 13C-NMR ca TG12.
Ph DEPT ca TG12.
XVI
Ph HSQC ca TG12.
Ph HMBC ca TG12.
XVII
PH LC 6. Ph khi lng v ph NMR ca TG13.
Ph khi lng ca TG13.
Ph 1H-NMR ca TG13.
XVIII
XIX
Ph 13C-NMR gin ca TG13.
Ph DEPT ca TG13.
XX
Ph HSQC ca TG13.
Ph HMBC ca TG13.
XXI
Ph khi lng ca TG15.
Ph 1H-NMR ca TG15.
XXII
Ph 13C-NMR ca TG15.
XXIII
Ph DEPT ca TG15.
Ph HSQC ca TG15.
XXIV
Ph HMBC ca TG15.
XXV
Ph 1H-NMR ca TG16.
Ph 13C-NMR ca TG16.
XXVI
Ph 1H-NMR ca TG19.
Ph 1H-NMR gin ca TG19

XXVII
/
Ph 13C-NMR ca TG19.
XXVIII
Ph DEPT ca TG19.
Ph HSQC ca TG19.
XXIX
Ph HMBC ca TG19.
XXX
Ph khi lng ca TG20.
Ph 1H-NMR ca TG20.
XXXI
Ph 13C-NMR ca TG20.
Ph DEPT ca TG20.
XXXII
Ph HSQC ca TG20.
Ph HMBC ca TG20.
XXXIII
Ph 1H-NMR ca TG21.

XXXIV
Ph 13C-NMR ca TG21.
Ph DEPT ca TG21.
XXXV
Ph HSQC ca TG21.
Ph HMBC ca TG21.
XXXVI
Ph 1H-NMR ca TG22.

XXXVII
Ph 13C-NMR ca TG22.
XXXVIII
Ph DEPT ca TG22.
Ph HSQC ca TG22.
XXXIX
Ph HMBC ca TG22.
XL
Ph 1H-NMR ca TG23.

XLI
Ph 13C-NMR ca TG23.
Ph DEPT ca TG23.
XLII
Ph HSQC ca TG23.
Ph HMBC ca TG23.
XLIII
Ph khi lng ca TG24.
Ph 1H-NMR ca TG24.
XLIV
Ph 13C-NMR ca TG24.
Ph DEPT ca TG24.
XLV
Ph khi lng ca TG25.
Ph 1H-NMR ca TG25.
XLVI
Ph 13C-NMR ca TG25.
Ph DEPT ca TG25.
XLVII
Ph HSQC ca TG25.
Ph HMBC ca TG25.
XLVIII
Ph 1H-NMR ca TG26.

XLIX
Ph 13C-NMR ca TG26.
Ph 13C-NMR gin ca TG26.

L
Ph HSQC ca TG26.
Ph HMBC ca TG26.
LI
PH LC 17. Kt qu xc nh hot tnh khng vi sinh vt kim nh.

Nng c ch 50% s pht trin ca vi sinh vt v nm kim nh - IC50 (g/mL)
Gram (+)
Staphylococ
cus aureus
TG1
TG2
TG3
TG10
TG11
TG12
TG13
TG15
TG17
TG18
TG19
TG20
TG21
TG22
TG23
> 128
> 128
> 128
> 128
109,63
> 128
>128
32,0
> 128
> 128
> 128
> 128
>128
> 128
>128
Bacillus
subtilis
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Gram (-)
Lactobacillus
fermentum
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Salmonella
enterica
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Escherichia
coli
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Nm mc
Pseudomonas
aeruginosa
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
(IC50 >128 g/mL: kt qu m tnh.)
LII
Aspergill
us niger
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Nm men
Fusarium
oxysporum
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
Candida
albicans
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
S.
cerevisiae
> 128
> 128
> 128
> 128
>128
> 128
>128
>128
> 128
> 128
> 128
> 128
>128
> 128
>128
LIII

LUANAN

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

LUANAN

Uploaded by

Copyright:

Available Formats

B GIO DC V O TO

TRNG TH THU HIN

NGHIN CU THNH PHN HA HC V HOT TNH

TRNG TH THU HIN

NGHIN CU THNH PHN HA HC V HOT TNH

Hng dn khoa hc: 1. PGS. TS. Phan Vn Kim

Trng Th Thu Hin

Trng Th Thu Hin

DANH MC CH VIT TT................................................................................. vi

2.3. Phng php xc nh cu trc ha hoc ........................................................31

4.2.24. Hp cht TG24: Stigmatsterol ............................................................123

Electron Spray Ionization Mass

Inhibitory dose at 50%

Human epidemoid carcinoma

Bng 29. S liu ph NMR ca TG22 v hp cht tham kho ..............................121

Hnh 31. Cu trc ho hc v cc tng tc HMBC chnh ca TG6. ......................72

Hnh 63. Ph 1H-NMR ca TG14...........................................................................100

triterpenoid, benzenoid v coumarin... Nhiu hp cht trong s th hin nhiu

Mc tiu ca lun n: Nghin cu lm r thnh phn ho hc ch yu

Ni dung lun n bao gm:

Tetradium austrosinense (Handel-Mazzetti) T. G. Hartley, 1981;

Tetradium calcicolum (Chun ex C. C. Huang) T. G. Hartley, 1981;

Tetradium daniellii (Bennett) T. G. Hartley, 1981;

Tetradium fraxinifolium (Hooker) T. G. Hartley, 1981;

Tetradium glabrifolium (Champion ex Bentham) T. G. Hartley, 1981;

Tetradium ruticarpum (A. Jussieu) T. G. Hartley, 1981;

Tetradium sambucinum (Blume) T.G. Hartley, 1981;

Tetradium trichotomum (Loureiro) Fl. Cochinch, 1790.

Cc loi trong chi Tetradium thng c thn bi hoc thn g, l di khong

1.1.2 Cc nghin cu v thnh phn ha hc ca chi Tetradium

methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone (42) v by limonoid

cht alkaloid t cy T ch ba (T. trichotomum) l: rutaecarpine (7), evodiamine

l 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (43), 1-methyl-2[(Z)-4-nonenyl]-4(1H)-quinolone (34) v 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]

[(6Z,9Z)- 6,9-pentadecadienyl]-4(1H)-quinolone (42). Tuy nhin, 43 l mt hp

1.1.2.1. Cc hp cht alkaloid

T.glabrifolium [109, 110]

[6, 8, 10, 58, 109]

25 1-Methyl-2- heptyl-4(1H)- quinolone

[9, 11, 12]

29 1-Methyl-2- undecyl-4(1H)-quinolone T. ruticarpum

[3, 9, 11, 12]

[3, 9, 10, 11, 12]

[3, 11, 12]

[3, 9, 10, 11, 12]

[3, 9, 10, 11, 12]

1.1.2.2. Cc hp cht triterpenoid

1.1.2.3. Cc hp cht limonoid

Bng 3. Cc hp cht limonoid c phn lp t mt s loi ca chi Tetradium

Limonin 17-O--D- glucopyranoside

[3], [4], [5],

1.1.2.4. Cc hp cht flavonoid

Bng 4. Cc hp cht flavonoid c phn lp t mt s loi ca chi Tetradium

1.1.2.5. Cc hp cht coumarin

Bng 5. Cc hp cht coumarin c phn lp t mt s loi ca chi Tetradium

[8, 109, 111]

1.1.2.6. Cc hp cht benzenoid

117 -Hydroxypropioguaiacone [109]

110 Gallic acid

1.1.2.7. Cc hp cht sterol

Bng 7. Cc cc hp cht sterol c phn lp t mt s loi ca chi Tetradium

1.1.2.8. Cc hp cht khc

1.1.3. Cc nghin cu v hot tnh sinh hc ca chi Tetradium

dng t bo ung th (GI50) ca hp cht 7. C th dng t bo rut kt HT-29 (31,6

1.1.3.3. Tc dng i vi h thn kinh