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Studi Kimia dan Farmakologi

Tumbuhan Obat Tradisional Indonesia

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 Beberapa senyawa kimia hasil isolasi dari Flores, NTT
Tumbuhan Obat “Dekar”, Caesalpinia major
O
O
R1
H H
H H
H
H
H

OH
OR2 OH
H3CO2C
Cesaldekarin a (7;0,86%), R1= H, R2 = Ac
Caesaldekarin c (10;0,06%)
Caesaldekarin b (8;0,05%), R1= H, R2 = H OH
Caesaldekarin d (9;0,01%), R1=OH,R2=Ac

O O H
OAc OAc
H H

H H O
H H H
AcO AcO
OH OH
12-oksi-7-okso-sandara
Caesaldekarin e (11; 0,06%) Caesaldekarin f (12; 0,09%) kopimaradiena (13;0,09%)

Hasil uji farmakologi :

- Caesakdekarin a (7), Inhibitory effect on mitogen
response of spleen cell (mice) IC50 = 10 mg/ml
- Inhibitory of Interleukin production, IC50 = 10 mg/ml 2
Chemical Transformation of caesaldekarin a into caesald. b and epoxide
Alkali treatment O

Caesaldekarin a H
H
(600 mg, 1.66 mmol) in MeOH (5.0 ml)
- Added 20 % KOH-MeOH (100 ml) OH
OAc
- Stirred at 40 oC for 20 min caesaldekarin a

(monitored by tlc) MW = 360

- Concentrated under reduced press
- Extracted with AcOEt/H2O x3

AcOEt ext.

- Washed with 5% HCl x3

10% NaHCO3 x3
brine x3
- Dried over MgSO4
- Evaporated in vacuo

Product 3
 Product
SiO2 column chromatography
(n-hexane-AcOEt = 7 ; 1)

caesaldekarin b epoxide
(370 mg,70%) (199 mg, 20%) O
MW = 318 MW = 300
H
O 70%
H

H OH
OH
H
20% KOH-MeOH caesaldekarin b

OH O
OAc
x x x caesaldekarin a
a b
H
epox H
20%

O 4
epoxide
Bromination Caesaldekarin a

(100 mg, 0,28 mmol) in CHCl3dry (5.0 ml)

- Added NBS (49.3 mg)
- Stirred at - 40~ 50 oC for 2 hr
(monitored by tlc)
- Work up in usual manner

O
caesal.a-NBS-1 caesal.a-NBS-2 Br
(49.0 mg, 40%) (15.0 mg, 7.5%)
H

O 40% H
caesaldekarin a-NBS-1
OH
H OAc
H
NBS/CHCl3

O
OH
OAc
caesaldekarin a
H
H
7.5%
caesaldekarin a-NBS-2
5
OH (dimer)
OAc
PCC oxidation
Caesaldekarin b Caesaldekarin b-PCC
(20 mg, 0,06 mmol)
(20 mg, 0,06 mmol) in CH2Cl2dry (1.0 ml)
in MeOH-ether = 10 :1 (4.0 ml)
- Added PCC (21.9 mg);
- Added NaBH4 (one microspatula full)
added CH2Cl2 dry (2.0 ml)
- Stirred at r.t for 20 min
- Stirred at r.t for 1 min
- work up in usual manner
- Filtered with florisil (in ether)
- SiO2 column chr. (n-hexane-AcOEt=5;1)
- evaporated
caesaldekarin b
- SiO2 column chr. (n-hexane-AcOEt=5;1) (19.5 mg; 100 %)
caesaldekarin b-PCC
(18.3 mg; 97%) MW = 316

O O

H PCC/CH2Cl2 H
H H
NaBH4/MeOH-ether
OH OH
OH O
caesaldekarin b caesaldekarin b-PCC
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 Acetylation of
Caesaldekarin b
caesaldekarin b
(10,0 mg, 0,03 mmol) in pyridine dry (0,1 ml)
- Added DMAP (3.0 mg)
- Added Ac2O (0.1 ml)
- Stand up at 40 oC for 30 min

- Poured an ice water, extracted with AcOEt x3

Wash up in usual manner

Caesaldekarin a (5.0 mg)

........%? O
O

H
H
H Ac2O/py; DMAP H

OH OH
OH OAc
7
caesaldekarin b caesaldekarin a
Reaction of caesal.b with m-CPBA
Caesaldekarin b

(202 mg, 0,64 mmol) in CH2Cl2 (5 ml)

- Added m-CPBA (108.2 mg; 80%)
- Stirred at r.t for 30 min

- Wash up in usual manner

SiO2 column chr. (n-hexane-AcOEt = 2 :3)

Product (165 mg, .....%)

O
O
O C H

H
H
H
m-CPBA/CH2Cl2 H

OH
OH OH
OH
caesaldekarin b 8