Phytochemwy, Vol 28, No 4, Pp 967-998, 1989 0031&9422/89

$3OC+OOO
Prlnted I” Great Bntaln 0 1989Pergamon Press plc

REVIEW ARTICLE NUMBER 43

XANTHONES FROM GUTTIFERAE

GRAHAM J. BENNETT and HIOK-HUANG LEE

Department of Chemistry, National Umverslty of Singapore, 10 Kent Ridge Crescent, Smgapore 0511

(Recerued m reusedform 1 November 1988)

Key Word Index-Guttlferae, xanthones; benzophenones, chemotaxonomy; blosynthesls.

Abstract-Since the last review m 1980, over eighty new xanthones have been isolated from the Guttiferae. These are
listed with reference to structure elucidation and synthesis. The distribution of xanthones is exammed m relation to the
taxonomic divisions of the Guttiferae Xanthone biosynthesis is discussed m the light of new biosynthetic results and
the various pharmacological properties of xanthones are summarized

INTRODUCTION temperate regions. According to Engler’s Syllabus [ 1l]

the family comprises six subfamilies (Table 1). The sub-
As the quest for new natural products continues, it
family Hypericoideae has been treated by some taxon-
becomes increasingly clear that xanthones are very re-
omists (notably Hutchinson [12]) as a separate family,
stricted in occurrence. The malority of natural xanthones
but the recent surge of interest m the chemistry of this
have been found in Just two families of higher plants-
group has led to the isolation of several prenylated
Guttiferae and Gentianaceae [l] Simple, oxygenated
xanthones, supporting its mclusion m the Guttiferae. The
xanthones occur in both famihes and are generally more
only related family m which xanthones have been found is
highly oxygenated in the Gentianaceae. Prenylated xan-
the Bonnetiaceae, which, m keeping with Thorn’s recent
thones are widely distributed m the Guttiferae but not
classification [13], is included in the Kielmeyeroideae
known in the Gentianaceae, and whereas O-glycosylxan-
subfamily in Table 1.
thones are common in the Gentianaceae [2], only two
Xanthones or the related benzophenones have been
have been reported from the Guttiferae
found in all the major and several minor genera of the
Xanthones occur sporadically throughout the remam-
Guttiferae. The approximate number of species [14], and
der of the plant kingdom. The Moraceae contain several
the number that have been found to contam xanthones 1s
Guttiferae-type prenylated xanthones and the Polygala-
given for each genus (Table 1). It appears from the
cae, simple hydroxy- and alkoxyxanthones [l]. C-Glu-
number of chemically investigated species (for three of the
cosylxanthones have been found m certain ferns, and in
larger genera), that a large proportion of the species
over one hundred species of higher plants [3], and fungi
contains xanthones. A species-xanthone index is mcluded
produce xanthones with substitution patterns character-
as an appendix
istic of then acetate derivation [4].
Several earher reviews have summarized the literature
on xanthones [S-lo], with emphasis on biosynthesis
Simple oxygenated xanthones
[7,8], synthesis [6,9] or phylogeny [lo]. In the last
review in 1980, Sultanbawa listed 95 xanthones from the The symmetrical nature of the xanthone nucleus, coup-
Gutttferae [l]. Smce then there has been a steady stream led with its mixed biogenetic origin m higher plants,
of reports in which more than 80 new xanthones have necessitates that the carbons be numbered according to a
been characterized and many known xanthones re-iso- biosynthetic convention. Carbons 14 are assigned to the
lated from ca 60 species of Guttiferae. acetate-derived ring A, (often characterized by 1,3-di-
The aim of this review is to summarize the recent work oxygenation) and carbons 5-8 to the shikimate-derived
on xanthones from the Guttiferae as a supplement to the ring B (e.g. 1,3,7,8_tetrahydroxy rather than 1,2,6,8). All
1980 review. The combined data will then be studied from higher plant xanthones appear to have S- and/or 7-
a chemotaxonomic pomt of view to determine if any oxygenation [S] and with this assumption, only xan-
patterns of xanthone distribution exist within the family, thones with 2,5(or 4,7)-oxygenation have alternative
and the imphcations of new biosynthetrc results will be names. In cases where only ring B ts oxygenated the
discussed. Structure elucidation, synthesis, and pharma- lowest numbers are used except in the biosynthetic
cology will also be covered. discussion [e.g. 2- rather than 7-hydroxyxanthone (l)].
Structural assignments are based mainly on ‘H NMR
and UV spectroscopy. Shifts of rmg or side-chain protons
DISTRIBUTION
due to acetylatton or alkylation of adjacent hydroxyls
The family Guttiferae numbers over 1000 species, and changes in the UV spectrum on addition of the usual
mainly confined to the tropics-the major exception shift reagents, are especially useful m determining substi-
being the genus Hyperrcum, which occurs widely in tution patterns. Confirmation of assignment may be

967
968 G J BENNETT and H-H LEE

Table 1 The family Guttlferae

SUB-FAMILY TRIBE GENUS NO. OF SPECIES*

Kielmeyeroideae Kielmeyereae Kielmeyera 20/9( 10)

Wahurea 8/l
Caralpeae CaraCpa 20/4
Haploclathra 413
(Bonnetiaceae) Bonnetia 18/l
Archytaea 2/l

Calophylloideae Calophylleae CalophylLum 110/21(32)

!Jesua(inc.Kayea) 4015
Wammea(inc. 50/5
Ochrocarpus)

Clusioideae Clusleae CLusLa 14514

Touomi ta 60/6
Garclnieae AllanbLackLa 8/l
GarcLnia 400/29(38)
PentaphaLangium 7/l

Rheedia 45/4

Moronoboideae Horonobea 7/l

Pentadesma 4/l
PLatonia l-211
Symphonia 20/l

Lorostemonoideae Lorostemon 3/2

Hypericoideae Cratoxyleae CratoryLum 6/2

Hypericeae Hypericum 400/18
VI smleae Harungana l/l
Psorospermum 40/l

Vismia 35/3

*Approx no. ofspecIes [14]/no ofspecIes m which xanthones and closely rdaled compounds have
been found Numbers m parentheses refer to number of species chemically mvestlgated

obtained by derivatlzatlon (sometimes not possible due to by a cycloaddltion reactlon between a dlene and a
the scarcity of material), although often synthesis IS benzopyranone [20]
necessary Mono-oxygenated xunthones. Two mono-oxygenated
The synthesis of xanthones has been revlewed [l&9]. xanthones (1 and 2, Table 2) have recently been isolated
The standard method is the Grover, Shah and Shah from seven species 4-Hydroxyxanthone also occurs in
condensation between an ortho-oxygenated benzolc acid Guttlferae. These compounds are now known to occur in
and a reactive phenol m the presence of phosphorous eight genera from three subfamihes. Notable 1s their
oxychlorlde and zinc chlonde [16] A recent vanation of absence from Clusloldeae (> 50 species investigated).
this method uses methylsulphonic acid and phosphorous Dioxygenated xanthones The majority of the recently
pentoxide m place of the above reagents [17]. Alter- isolated dioxygenated xanthones (Table 3) are from spe-
natively, benzophenones, prepared by Friedel-Crafts cies of the Hypencoldeae, reflecting the recent interest m
acylation [18], may be converted to xanthones by dehy- this subfamily Dloxygenated xanthones are however,
drative or oxldatlve cyclizatlon. Two other methods have also common m species of Calophyllum, Mammea and
appeared recently. The nucleophihc addltlon of salicyhc Mesua and found in all subfamilies 1,7-Dlhydroxyxan-
acid denvatlves to p-benzoqumones has been used to thone (4), has now been Isolated from 40 species of
prepare a series of 1,4(or 5,8)-dlhydroxyxanthones [19], Guttlferae The 2,5-dloxygenation pattern of xanthones 5
and 3-hydroxyxanthone has been prepared in 50% yield and 10 IS new from nature
 Xanthones from Guttlferae 969

Table 2 Mono-oxygenated xanthones

2-Hvdroxvxanthonefl) 2-lathoxvxanthone(21

CalophyLlum zeylantcum Kosterm.[21] Caratpa pstdtfolta Ducke [29]

Hypertcum baleartcum L. [22] Hypertcum mysorense [27]

Hypertcum canartensis L. [24] Vtsmta guaramtrangae Huber [28]

Hypertcum ertcotdes L. [25]

Hypertcum mysorense [26.27]

Vtsmta guaramtrangae Huber [ZS]

*First reported occurrence m nature

tFlrst reported occurrence in Guttlferae.

Table 3 Dioxygenated xanthones

1.5-DibvdroxvxanthoneC31 I-Hvdtoxv-7-¤ethoxvxanthonef71

CalophyLLum zeylanicum Kosterm.[Bl] Bonnetta stricta (Nees) Ness

Mart. [31]
Garctnta xanthochymus Hook. f. [30] HaplocLathra paniculata (Mart.)
Benth. [33]
1.7-DihvdroxvxanthoneC4IfEuxanthonel Haploclathra uerttctLLata Ducke[29]

Bonnetta strtcta (Nees) Ness & Hypertcum mysorense [26]

Mart.[31]
CaLophyllum zeylantcum Kosterm.[21] Mahurea tomentosa Ducke [29]

Carctnta indtca Choisy [50]

Vtsmta guaramirangae Huber [28]
Garcinta xanthochymus Hook. f.[30]
2-Hvdroxv-1-methoxvxanthone[f%I*
HaplocLathra uerttctlLata Ducke[29]

Hypericum baleartcum L. [22] Vismta guaramirangae Huber [28]

Hypertcum canartensls L. [24] 2-Hvdroxv-3-methoxvxanthone(91

Hypertcum ertcotdes L. [25] *HyperCcum mysorense [ZS]

Hypertcum mysorense [26.27]] 2-Hvdroxv-5-methoxvxanthoneflOl_

Kahurea tomentosa Ducke [29] *Hypertcum androsaemum L. [34]

Vtsmta guarantrangae Huber [ZS] Nypertcum canartensts L. [24]

2.5-Dihvdroxvxanthonef51 3-Hvdroxv-P-methoxvxanthonefllk

*Hypertcum canartensts L. [24] Hypericum androsaemum L. [34]

2.3-DImethoxvxanthonal6l. Hypericum balearicun L. 1223

*Hypertcum mysorense [27.32-J Psorospermum febrtfugum Sprach [36]

Vtsrta guaramtrangae Huber [28]

Trioxygenated xanthones. Twenty trioxygenated xan- (17), 1,4,7- (19) and 2,3,5- (27), and xanthones 33 and 34
thones, of which nine are new natural products, are are the first trimethoxyxanthones from the Guttlferae.
shown in Table 4. Novel oxygenation patterns are 1,5,8- Two 1,2,Strioxygenated xanthones (12 and 14) have been
970 G J BENNETT and H-H LEE

Table 4 Trloxygenated xanthones

I-Hvdroxv-3.5-dilethoxvxanthonel23)

*Carc~nn xanrhochymus Hook f c301 HapLoclathra pantculata (Mart )

Benth [33]

1.3-Dihvdroxv-2-methoxvxanthonell3) 1-Hvdroxv-6.7-dimethoxvxanthone[24)_

Hypericum mysorense [26]

1.5-Dihvdroxv-2-aethoxyxanthonell4) l-Hydroxv-7.8-dimethoxyxanthone(251

*Carc~n~u xanthochymus Hook. f c301 Haploclathra pan~culata (Mart )

Bench [33]

1.5-Dihvdroxv-3-methoxvxanthone~l5~ 2-Hydroxv-3,4-diaethoxvxanthone(26)

Garcinia ranthochymus Hook f.[30] Hypericum canarLensis L 1241

Haploctathra Lieantha (Benth ) Hypericum sampson~t Hance [39]

Benth C361
Haploclathra paniculata (Mart ) KteLmeyera rubiflora Camb c4o1
Benth [33]
Vismia guaram~rangae Huber [28] *Kielmeyera spec~oso St.Hlll [40]

1.5-Dihvdroxv-6-methoxvxanthone(l6r 3-Hvdroxy-2.5-dilethoxvxanthonel27)

*
rouomtta excelsa Andrade-Lima et *Hypericum androsaemum L c341
G Marlz [37]
1.5-Dihvdroxv-8-methoxvxanthone(l7)_ 4-Hvdroxv-2.3-dilethoxyxanthone0

*VLsmia guarnmirangae Huber [28] Cara~pa grand~fLora Mart. [29]

1.6-Dihvdroxy-5-lethoxyxanthone/ls) 5-Hvdroxy-1.3-di=ethoxyxanthone[29)
‘IBuchanoxanthone)

Calophyllum zeyZanLcum Kosterm [21] Haploclathra panlculata (Mart.)

Benth ‘c331
Touomita excelsa Andrade-L.lma et 1.3.5-Trihvdroxvxanthonef301
G Marlz [37]
1.7-Dihvdroxv-4-rethoxvxanthonefl91 Carcinia xanthochymus Hook. f c3o1

*VtsmCa guaram~rangne Huber [28] 1.3.7-Trihvdroxvxanthonef31)_

/Gentisein)
1.7-Dihvdroxy-6-methoxvxanthonef201 Haploclathra paniculata (Mart 1
Benth t-331
*Touomita excelsa Andrade-Lima et Hypericum degentf Bornm. [41]
G Marlz [37]
1.7-Dihvdroxv-8-=ethoxvxanthone[21) 1.6.7-Trihvdroxyxanthonef32)

Bonnetia stricta (Nees) Ness & Ptntonia instgnis Mart [29]

Mart [31]
Haploclathra [leantha (Benth )
Benth. [36]
HapLoclathra panicuLata (Mart )
t Haploclathra paniculata (Mart 1
Benth. [33] Benth c331
5.6-Dihvdroxv-1-lethoxvxanthone[221 2.3.4-Tri=ethoxvxanthone[34)

*Touomtta excelsa Andrade-Lima et *Hypericum ericoides L c251

G.Mariz [373

reported from Garcinia xanthochymus, but their physlcal wood of Tovomita excelsa, were assigned a l,S,&dihy-
data have not been pubhshed. droxymethoxy structure [37]. Two of these (l&18) were
Three of the four xanthones isolated from the trunk known compounds, whereas the I-methoxy structure (22)
 Xanthones from Guttlferae 971

Table 5. Tetra- and pentaoxygenated xanthones

1.3-Dihvdroxv-5.6-dimethoxvxanthone 2-Hvdroxv-5.6.7-trimethoxvxanthone
iLeiaxanthone)(35) (43)
‘Haploclathra Lieantha (Benth ) *Hypericum erLcotdes L c251
Benth [36]
1.5-Dihvdroxv-6.7-dimethoxvxanthone 3-Hvdroxv-1.2.4-trimethoxvxanthone
I36) I44)
Caraipa grandLfLora Mart c291 *Psorospermum febrLfugum Sprach [35]

Caraipa pstdifolla Ducke [29] 3-Hvdroxv-1.5.6-trimethoxvxanthone

(45)
Caraipa ualioi Paula [29] HapLocLathra lieantha (Benth )
Benth [36]
TouomLta brasiliensis Walp c421 7-Hvdroxv-1.3.8-trimethoxvxanthone
JAnthaxanthone)(46)

1.6-Dihvdroxv-5.7-dilethoxvxanthoxvxanthone *HapLocLathra Lieantha (Benth )

(37) Benth [36]

Hypericum canariensis L [24] 1.3.5.6-Tetrahvdroxvxanthonel471

I.?-Dihvdroxv-3.8-dimethoxvxanthone Hyperrcum androsaemum L c341

[Gentiaculein)(381
t’
HapLocLathra Lieantha (Benth ) 1.3.6.7-Tetrahvdroxvxanthone[481
.Benth [36] /Norathvrioll

HapLocLathra paniculata (Mart ) Cratorylum prunLfLorum Kurz CL301

Benth. [33]

2.5-Dihvdroxv-1,6-dimethoxvxanthone CarcLnLa mangostana L. [46]

G!.zQ
*Garcinia thaaiteslt Pierre [43] Hypericum androsaemum L. [34]

3.7-Dihvdroxv-1,8-dimethoxvxanthone Hypericum aucherL Jaub et

(40) Sprach. [47]
*HapLocLathra pan~culata (Mart.) 1.3.5-Trihvdroxy-6-methoxvxanthone
Benth [33] 149)
3.8-Dihvdroxv-1.7-dimethoxvxanthone HaplocLathra lLeantha (Benth )
17 Benth. [36]
t
HapLocLathra panLcuLata (Mart.) 1.5.6-Trihvdroxv-3-methoxvxanthone
Benth [33] w

5.6-Dihvdroxv-1.3-dimethoxvxanthone ‘Hypertcum androsaemum L. [34]

fFerrxanthonelf421
HapLocLathra Lteantha (Benth ) l-7.8-Trihvdroxv-6-methoxvxanthone
Benth. [36] (51)
*Hesua ferrea L. [23] *Archytaea multiflora Benth. [31]

2.4.5-Trihvdroxv-1-methoxvxanthone
I_

*Garctnia mangostana L. [83]

3.8-Dihvdroxv-1.2.4-trilethoxvxanthone(531

*Psorospermum Febrifugum Sprach c351

was new. An unambiguous synthesis of 22 has been
completed by the methylation of 1-hydroxy-5,6-diben-
zyloxyxanthone followed by debenzylation, and the prod-
uct shown to be different from the.natural compound
[38]. 4,5-Dlhydroxy-3-methoxyxanthone IS suggested as
a likely alternatlve structure
The sodmm acetate induced shifts m the UV spectrum
of a 2,3,4-hydroxydlmethoxyxanthone from Kielmeyera
species, led to the assignment of the more acidic 3-
hydroxy structure. However, the 13C NMR spectrum has
indicated that both methoxy groups are di-ortho-substi-
tuted and that therefore the structure should be 2-
Hydroxy-3,4-dlmethoxyxanthone (26) [40]. Conse-
quently, the structure of a xanthone from Hypericum
canarlensn should also be revised to 26, as in Table 4.
Ten xanthones have been isolated from the roots of
Vismia quaramirangae [28] Based mainly on ‘H NMR
spectroscopy, one of the three new xanthones was as-
972 G J BENNETTand H -H LEE

signed the structure of 1,7-dlhydroxy-4-methoxy- thone (53, Table 5) IS related to 44 from the same plant,
xanthone (19X rather than the 2-methoxy alternative and brings the total number known to five
that was indicated by a positive Gibbs test. Two para-
dloxygenated analogues also gave positive Gibbs tests,
Alkylated xanthones
suggesting that this test IS unrehable m certain cases
Tetraoxygenated xnnthones The newly Isolated tet- Alkylated xanthones in Guttlferae are usually mono-
raoxygenated xanthones are shown m Table 5. In the first or dl-C,-substituted The C, group may be 3-methylbut-
mvestlgatlons of the genus Haploclathra, three species 2-enyl (as m 54), or less often l,l-dimethylprop-2-enyl (as
have yielded 17 different xanthones [29, 33, 361. These m 89), and these are frequently cyclized with ortho
include four 1,3,5,6- and four 1,3,7,8_tetraoxygenated hydroxyls giving 2,2_dimethylpyrano (or dihydropyrano),
xanthones, the latter being common in the Gentianaceae 2,2,3_trimethylfurano (possible artefacts), or rarely 2-
Xanthone 35 has been synthesized [44] and shown to be lsopropenyldihydrofurano compounds Occasionally,
identical to a compound from Centaur-turn lmarlfolium, hydroxylatlon or hydration of the side chain occurs C,,
but to differ somewhat from the Haploclathra xanthone. substltuents, m which two prenyl groups are Joined
Several unusual oxygenation patterns have been found. together, Include geranyl (as m 112) and lavandulyl (as in
The stem bark and timber of Garcmla thwaltesl ylelded 115)
2,5-dlhydroxy-1,6-dlmethoxyxanthone (39), and the The oxygenation patterns of alkylated xanthones are
structure of 2-hydroxy-5,6,7-trimethoxyxanthone (43), less diverse than m the unalkylated compounds Four
isolated from Hyperlcum erzcotdes [24], has been con- patterns predominate: 1,3,5-, 1,3,7-, 1,3,5,6-, and 1,3,6,7-
firmed by synthesis (Scheme 1) [45] A 1,2,4,5_tetraoxy- Di- and pentaoxygenated compounds are rare.
genated xanthone, BR-xanthone-B (SZ), has been Isolated Mono-C,-trloxygenuted xunthones Fractlonatlon of
from the fruit of Garcrma mangostuna. the cytotoxic ethanol extract of the roots of Psoros-
The mcluslon of Archytaea (Bonnetlaceae) in the sub- permumfebrfigum led to the lsolatlon of the antl-leuk-
family Klelmeyeroideae IS supported by the lsolatlon of a aemlc xanthones, psorospermm (57, Table 6) and its
1,6,7,8_tetraoxygenated xanthone (51) from Archytaea chlorohydrm (58) [Sl, 521. Their ready mterconverslon
multrjiora [31] This oxygenation pattern IS only known suggested a possible artefact Tandem mass spectrometry
in other three species, two of which belong to this has confirmed that psorospermm IS a natural product,
subfamdy while the posslblhty that 58 IS an artefact has not been
Pentaoxygenated xanthones. These compounds are rigorously excluded [53] The other derivatives (59-61),
rare m the Guttiferae but common m the Gentlanaceae show no anti-leukaemlc properties The absolute stereo-
The new compound, 3,8-dlhydroxy-1,2,4-tnmethoxyxan- chemistry of psorospermm has been determined as

Reagents ( I ) AlC13/ ether, ( II) Me,NOH / reflux, ( ~1) H,, Pd / C

Scheme I
 Xanthones from Guttlferae 913

Table 6 Mono-C,-tnoxygenated xanthones

w (56) 6-Deoxviacareubin
CaLophyLlum zeylantcum Kosterm.[21]

OH

3, e

0 OMe
(57) R=
7.s
4.
0

Me
; PSOrOSDerriU (2.R.3.R)

(2.R.3.S)
(59) R=
‘r< OH
CH,Cl
e
(59) R= (2.R.3.R)
r" OH
CH,OH

Me
(60) R = : 3’ .a’-DeOXvD SOTOSD‘ZrliI,
Y I

(61) R= ""H (5-O-Methyl)

l<o
Me

*Psorospermum febrifugum Sprach.

C51.52.541

0 OH

(62) Rheediachro-enoxanthone
Rheedia brastliensis (Mart.)
Pl. and Tr.[58]
*Rheedia gardnerlana Pl. and Tr.[59]

(63) RI = H. R2 = OH: Hvmericanarin

*Hypericum canariensis L. [24]

(64) R, = OH, R, = H; livperxanthone

1 *Hypericum sampsonit Hance [39]

2’R,3’R by an ORD, ‘H NMR and TLC comparison with Progress towards a total synthesis of psorospermm has
analogous epoxides denved from rotenone [54]. been made by the enantioselective preparation of the
A stereoselective synthesis of 5-methyl-( -!-)-2’R,3’S- 2’R,3’R-dlhydrobenzofuran (66) [56] A synthesis of the
psorospermin (65) has been completed and 1s shown m 5-methyl-1’,2’-dehydro derivative of 3’,4’-deoxypsoro-
part in Scheme 2 [55]. The final step in the synthesis spermm (60) has also been reported [57].
involves two consecutive displacements, producing a Rheediachromenoxanthone (62) and hyperxanthone
racemlc mixture of the 2R’,3’S and 2’S,3’R epoxides (65). (64) appear to be derived from tetraoxygenated xan-
974 G J. BENNETTand H -H LFE

Reagents ( I) Os04/Na104, dioxane / Hz0 (11) PIlsP=C(Me)CO,Et.

benzene (m) LlAIH./THF (IV) MCPBA, CH2C12 (v) MsCL/py
(VI) H,.Pd/C (vu) KO’Bu

OMe

Me0

66
Scheme 2

thones by nuclear reduction at the 3- and l-pontions
respectively In fact, 64 occurs with the expected precur-
sor, toxyloxanthone B (82) m Hyperuzum sampsonu The
unusual 4,6,7- (or 2,3,5-?) oxygenation pattern of hyperi-
canarm (63) IS otherwlse only known in 27 from Hyper-
icum androsaemum. The structures of 63 and 64 are
supported by significantly different physical data
Dl-C,-trroxygenated xanthones Garcmone A from
Garcima mangostana was asslgned a novel 1,3,6-tnhy-
droxy structure (68, Table 7), an oxygenation pattern
unknown m the Guttiferae However, the synthetic sub-
stance, prepared by the prenylatlon of 1,3,6-trlhydroxy-
xanthone, showed httle similarity with the natural com-
pound [66].
The stem bark of Garcmla quadrfarta produces xan-
thone 69, which shows a rare prenylation, para, rather
than ortho to a hydroxyl group. 6-Deoxy-y-mangostm
(70) has been isolated from the seed arils of Garcinza
mangostana fruit and IS a possible biosynthetic precursor
to mangostm (70; R, = Me, R, = OH), the major metab-
olite from the same plant (see Biosynthesis).
The stem bark of Calophyllum walker1 contains xan-
thones 74 and 7678 The hydroxymethyl group in thwal-
teslxanthanol (77) was located by mild acetylatlon
Shielding of H-3” was observed, while H-3’ was un-
affected [65]. The 2-lsopropenyldlhydrofuran group of 78
IS otherwise only known (without the hydroxy) m 3’,4’-
deoxypsorospermin (60) The cts configuration of 78 was
asslgned from the 6 Hz couplmg between the 2” and 3”
protons The 3” proton was also coupled to H-6 and
strongly deshlelded, suggestmg that It IS almost m the
same plane as the xanthone nucleus
Mono-C,-tetrahydroxyxanthones Xanthone 79 (Table
8) IS the second 1,3,5,8-tetra-oxygenated xanthone from
G. mangostana, the other bemg gartanm (79; R, =H, R,
=prenyl). This oxidation pattern IS otherwise unknown
m the Guttiferae but common m the Gentianaceae Three
2-prenyl-3-methoxyxanthones (54. 55, and 79) have been
 Xanthones from Guttlferae 975

Table 7 Dl-C,-tnoxygenated xanthones

(67) R, = OH, Rz = H. CDesoxvKartanin

RheedCa brasiliensis (Mart.)

Pl. and Tr
Rheedia gardnerLana Pl and Tr

(68) RI = H. R, = OH: Garcinone &

*Carcinia mangostana L. [61]

(69) 4.8-Dif3rmethylbut-2-envlj-1.3.5-

trihvdroxvxanthone

*Garcinta quadrifaria Bail1

ex Pierre [62]

(70) R,=R,=H; 6-Deoxv-T-¤angostin

*CaLophyLLum thoaitesi Pl. and Tr C631

Garcinta mangostana L [49]

(71) R,=H. R,=Me: Calcocalabaxanthone

16-Deoxvraneostin)

CalophyLlum bracteatum Thw. [63]

*CalophylLum calaba var.calaba L

[63.64]

0 OH

(72) ‘frapezifolixanthone

CaLophylLum calaba var. calaba L [63j

Rob ;;c:;
(73) ._;;;-=-;;,
Calophyllum

Calophyllum
calaba

zeylanicum
var.
c4g,
calaba

Kosterm.[Bl]
L.[643

(74) R = H ; Deaethylcalabaxanthone

*Calophyllum walkeri Wight [SS]

Garclnta mangostana L. [49]

Pl.and Tr.[63]
976 G J BENNETT and H-H LEE

Table 7 Conmued

‘1 (76) R = Me; Thraitesixanthone

Calophyllum walker-t Wlght [65]

(77) R = CH,OH. Thraitesixanthonol

*Calophyllum walker-L Wight [65]

y.2I_ (78)

*Calophyllum walker-L Wlght [65]

Table 8 Mono-C,-tetraoxygenated xanthones

-
(79) R, = Me, R2 = H
1.5.STrihvdroxv-3-methow-2-
p
*
Car-CirlLQ mangostana L cf371

0.H R,

(80) 1.3.6.7-Tetrahvdroxv-8-(3-
methvlbut-2-envl)xanthone

*Hypericum androsaemum L [34]

H

0 OH

HoJc)IYKk
(El) Jacareubin

Calophyllum zeyZanLcum Kosterm [213

(82) Toxvloxanthone B

t HyperLcum nndrosaemum L II341

Hypertcum sampsonir Hance [39]

found in Garcrnza mangostana The 3-methoxy group
prevents further prenylatlon m the 4-posItIon, however
the presence of a methylatmg enzyme does not preclude
4-prenylatlon as IS shown by the presence of 67 m the
same plant
Toxyloxanthone B (82), first found from the Moraceae,
has been Isolated from Hyperlcum androsaemum together
with its probable blogenetlc precursor (80)
DA’,-tetraoxyqenated xanthones While the xan-
thones m this category (Table 9) are more numerous than
 Xanthones from Guttlferae 977

Table 9 DK,-tetraoxygenated xanthones

(83) Xanthone I&

*Vtsnia gutneensts (L.) Choisy [68]

(84) 7-PrenvlMcereubin

*Rheedta gardnertana Pl.and Tr.[60]

OH

(85) R = 3-Methylbut-2-enyl; Xanthone Ei

*Vismia gutneensts (L.) Choisy [SS]

(86) R = l,l-Dimethylprop-2-enyl;

Racluraxanthone

Garctnta oualtfolta 0 iv. [69]

t
Rheedia benthaatana P . and Tr.[70]

OH R
Rheedia brasiLtensts ( Mart.)
i l.and Tr.[581
Rheedia gardnertana PI. and Tr.[59]

0 OH
(87) Pvranojacereubin

Rheedta brastltensts (Mart.)

Pl.and Tr.[58]
*Rheedta gardnertana Pl.and Tr.[GO]

dH

(88) Rheediaxanthone h

*Garctnta denstuenia Engl. [71]

Garctnta staudttt Engl. [62]

Rheedta benthaniana Pl. and Tr. [703

Rheedta brastltensts (Mart )

Pl. and Tr. [58]
Rheedta gardnertana Pl. and Tr. [59]

0 OH Rheediaxanthone B
(89)
*Rheedta benthnmiana Pl. and Tr. [701

Rheedia brastltensis (Mart.)

Pl. and Tr. [58]
Rheedta gardneriana Pl and Tr. [591
978 G J BENNETTand H-H LEE

Table 9 Contwmd

0 /

(91) Rheediaxanthone C

*Rheedia benthamiana Pl. and Tr c701

Rheedia brasiliensis (Mart )

Pl and Tr
Rheedia gnrdnertana Pl. and Tr ;ztJ ?

(92) *Rheedia brasiliensrs (Mart.)

Pl.and Tr [58]

AH cg3)
*Rheedta brasiliensts (Mart.)
Pl.and Tr [SS]

0 OH

(94) *Rheedia brasiliensis (Mart )

Pl and Tr.[58]

0 OH

(95) RI= Me. R, = H: lanplexanthone

*Touomita mangle G Maritz [73]

\ (96) Garcinone B

*Garcinin mangostana L [61.147]

 Xanthones from Gutnferae 979

Table 9 Contmued

(97) *carcinta mQngostQnQ L. [74]

(98) 3’.4’-Dihydro 93; J-Isomanvostin

*Carcinia mangostana L. [49]

(99) R = H; Garcinone C

*Carctnia mangostana L. [61]

(100) R = Me: Garcinone D

*
Carctnta mangostana L. [75]

(101) 3’.4’-Dihydro 96; 3-Isoraneostin

Hvdrate
*Garcinia mangostana L. [49]

(102) R = -C=CHMe,: 1-Isoranvostin

(103) R = -CH,C(OH)Me, : 1-Isomaneostin

H Hydrate

*Garcinia mangostana L. [49]

(104) BR-xan thone-A

*CarcCnia mangostana L. [SJ]
\

the monoprenylated compounds, there is little structural
variation This IS due m part to the fact that most of these
xanthones have been Isolated from only a few species
of the closely allied genera Garcwa and Rheedia. Dia-
lkylated xanthones, especially dlpyrano compounds, give
rise to doubly-charged Ions in their mass spectra due to
the simultaneous loss of two alkyl fragments [SS]. Apart
from macluraxanthone (86), which is known from a
Moraceae species, all the xanthones in Table 9 are new
natural products.
A dipyranoxanthone from Garcinta densivenia was
originally assigned the linear structure of pyranojacereu-
bm (87) on the basis of the size of the diamagnetic shift of
H-4’ upon 0-acetylation [71]. Subsequently, when a
similar compound was isolated from Rheedia gardneriana
and the two compounds compared, the structure of the
G. densivenla xanthone was revised to that of rheediaxan-
thone A (88), and the new compound assigned the
structure of pyranojacereubm (87) [60]. This example
serves to highlight the problem of differentiating between
substituents at the 2- and 4-positions. Upon acetylation,
H-4’ of 87 was deshielded by 60.26 (expected -60.30),
compared to 60.19 for H-4’ of 88 [60].
Compounds which contain a 1,1,2-trimethyldihydro-
furan nng are possible artefacts due to the ease with
which the parent l,l-di~ethylallyl group cychzes with an
ortho-hydroxyl. Rheediaxanthone B (89) and xanthones
90 and 94 are optically active and should therefore be true
natural products; however rheediaxanthone C (91), al-
though also optically active, is thought to be an artefact of
89 [70].
Nine of the xanthones in Table 9 were isolated from
Rheedta brasiliensls and are biogenetically closely related
(eg. 92-94). The location of the methoxyl in manglexan-
thone (95) was confirmed by its 13C NMR chemical shift
(> S60), indicating di-ortho-substitution [70]. Therefore
95 is apparently different from tovopyrifolic A (95; R,
= H, R, = Me) which IS found m the same genus [76].
During the last eight years an equal number of papers
have described new xanthones from Garcinia mangostana.
Those shown in Table 9 all contain the 1,3,6,7-tetra-
oxygenation pattern and are cychzed or hydrated deriva-
tives of the major metabolite, mangostin (70; R, = Me, R,
= OH) or y-mangostm (70) R, = H, R, =OH). The
chromanoxanthones (98 and 101-104)had been syn-
theslsed previously by the p-toluenesulphonic acid cata-
lysed cyclization of mangostin [77]. Whereas this reagent
gave both linear and angular chroman rings, methanolic
HCl gives only the linear product [78].
Dlmethylmangostin (106), which may be selectively
demethylated to give the natural mangostins, has been
synthesized by Lee (Scheme 3) [79]. The problem of
980 G J BENNETTand H -H LEE

186 R = Me
187 R = H

Reagents (I) TFAA/CH2C12 (n)H2,Pd/C (ui) CH2N2 (IV) Me.,NOH/py (v) BC’L~/CHICl,
(n) Mel/K#ZO, (vu) McCOCI/K&YOB (viu) LlCL/DMF (XI) KO’Bu/DMSO
Scheme 3

selective prenylation m the 2- and 8-posltions was over- Calophyllum wightuznum produces a palmltic acid
come by the preparation of the dichromanoxanthone clathrate which yielded a xanthone named wightlanone
(105). Ring openmg was accomphshed with boron trl- [81]. A .5,5-diprenyl structure was proposed. However, on
chloride to give a dlchlorlde which underwent dehydro- comparison [21], it was found to be identical with a
chlormatlon with hthmm chloride m DMF, producing sample of zeyloxanthanone (117) isolated from Calo-
106 AlternatIvely, treatment of the dichloride with pot- phyllum zeylumcum Gamboglc acid (118) has been re-
assmm-t-butoxlde m DMSO gave p-mangostm (107) isolated from Garcrma hanburyl together with a new
Trr-C,-tetraoxygenated xanthones. Five xanthones of derivative, neo-gamboglc acid (119) [82]
this type are now known, and the two new ones are shown
m Table 10. The structure of garcmone E (108) 1s tenta-
Xanthone glycosrdes
tive, and based mainly on the formation of a tnchromano
compound with methanohc HCl [78] The C-glucosylxanthones, mangiferm (120; Table 12)
The novel ring B substltutlon pattern of nervosaxan- and lsomangiferm (121) have been found m several spe-
thone (109) was suggested by the deshlelded methylene of cies of Hyperrcum and Cratoxylum prumforum but are
one of the prenyl groups, placmg It peri to the carbonyl, not known In the rest of the famdy. The taxonomic
and the ‘H NMR resonance of the single aromatic pro- significance of thrs will be discussed later There are only
ton [72] The arrangement of the 2- and 4-substltuents two examples of 0-glycosldes in Guttlferae (122, 123),
was determined by an ‘H NMR study of the tn- and although neither has been properly characterized Both
tetra-acetates 0- and C-glycosylxanthones are common m the Gentlan-
Dl-C,-pentaoxygenated xanthones The first natural aceae [2]
examples of thn type are xanthones V, (110)and V,, (111)
(Table 10) from Vismla qumeensts They are the 7-meth-
Xanthonohgnoids
oxy derlvatlves of xanthones V, (83) and V,, (85) (Table
9) Together these constitute the only occurrences of Kielcorm was first isolated from Klelmeyera species,
prenylated xanthones m the genus Vtsmla and Its structure has been defined as a racemate of the two
More complex xanthones. Garcrma pyr$era shows a 5,6-trans isomers (124)[SS] It has recently been isolated
link with G. cowa and G. rubrn by producing 8-geranyl- from several Hypericum species and Vtsmia guaramlran-
1,3,6,7_tetraoxygenated xanthones (112-l 14; Table 11) gae. The other xanthonohgnolds m Table 13 also have the
[72] The optically active maculatoxanthone (115) IS the trnns configuration and are optically inactive.
first xanthone with a lavandulyl side chain, although this BIogenetIcally, xanthonohgnolds are thought to be
arrangement is found m three benzophenones-tovo- formed by the coupling of a cmnamyl alcohol with an
phenones A and B (141,142) and xanthochymol (144). ortho-dlhydroxyxanthone Klelcorm and 2.3,4-(or 5,6,7)-
Calozeyloxanthone (116) contams a novel C,, arrange- trloxygenated xanthones co-occur m Hypericum caly-
ment, presumably a cychzed geranyl group cmum and H. ertcoldes as well as m three Ktelmeyera
 Xanthones from Guttlferae 981

Table 10 Trl-C,-tetraoxygenated and Dl-C,-pentaoxygenated xanthones

(108) Garcinone E

*Carctnta nangostana I,. [78]

(109) Uervosaxanrhone

*Garctnta neruosa Miq. [72]

0 OH

(110) Xanthone E

*Vtsmta gutneensts (L.) Choisy [683

(111) Xanthons $,,

*Vtsmta gutneensts (L.) Choisy [68)

species. The 1,5,6,7_tetraoxygenated candensins A and C Benzophenones

(125, 126) are found alongside similarly substituted xan-
Benzophenones are of interest as they have been Impli-
thones in the two Cararpa species and H. canariensls
cated in xanthone biosynthesis. Simple benzophenones
Furthermore, syringaresmol (129), a likely precursor to
are rare m the Guttiferae. They have been found in the
the C& moiety of candensins A and C, has been isolated
heartwood of five species (Table 14t_usually with anal-
as the diacetate from Vtsmra quaramirangae.
ogous xanthones. For example, maclurm (134) occurs
Klelcorin (124) has been synthesized by two different
with 1,3,6,7-tetrahydroxyxanthone (48) in Garcinia
routes [91,92] One involves the blomlmetic coupling of
mangostana, with 48 and 1,3,5,6-tetrahydroxyxanthone in
2-methoxy-3,4_dihydroxyxanthone (130, Scheme 4) and
Symphonia globulifera and with xanthochymol (144) in
comferyl alcohol (131) [91] crs-Klelcorin (124, 5,6-crs)
Garcmra xanthochymus.
was a mmor product.
Candensinb and hyperlcorin from Hyperlcum canar-
lenses and H. mysore&- respectively, have been assigned
Prenylated benzophenones
the same structure (127) and their ohvslcal data comnare
reasonably well. An isomer of kielcorin, named kielcbrin These compounds shown in Table 15, may be divided
B has been ldentlfied in Kielmeyera corlacea and tenta- into two groups, true benzophenones (M-142) and those
tlvely assigned structure 128. with reduced A rings, the so-called polyisoprenylated
982 G J BENNETTand H-H LEE

Table I1 More complex xanthones

(1121 R = H. Rubraxanthone

(113) R = 3-Methyl-2-butenyl:*Iscoranin

(114) R = 3-Methyl-4-hydroxy-2-butenyl;

*Isocoranol

Garctnta pyrtfera Ridl. [72]

H

(116) Calozevloxanthone
*
Calophyllum zeylantcum Kosterm.[21]

(117) Zevloxanthonone /liahtianone)

Calophyllum aightiagnum T Anders [811

*Garctnia hanburyi Hook f [827

benzophenones (143-148) Of the former group, five Garclnia /da, shows broad antlmicroblal actlvlty [102]
contam unsubstituted B rings, and therefore have no There has been some controversy regardmg the struc-
known xanthone analogues. The vlsmlaphenones tures of the four closely related compounds contaimng a
(136-139) have been synthesized by the prenylatlon of blcyclononene motety (144-147). The X-ray determined
suitably substituted benzophenones [98-1001. Tovo- structures of xanthochymol (144) and lsoxanthochymol
phenones A and B (141, 142) contam the rare lavandulyl (146) are shown m Table 15 Cambogm (147) was shown
side chain, aqd koianone (143) from the edible fruit of to be the antipode of the latter and cambogmol (145),
 Xanthones from Guttlferae 983

Table 12. Xanthone glycosldes

&
(120) R,=B-D-Glucopyranosyl, R,=H: (121) R,=H. Rs+-D-Glucopyranosyl;

Isomaneiferin

Cratoxylum pruntflorus Kurz. [130] Cratoxylum pruntflorum Kurz. [130]

Hypericum aucheri Jaub et Hypericum boissieri Petrovic [85]

Sprach 1471
Hypertcum barbatum Jack [S4] Hypertcum hirsutum [87]

Hypericum botssieri Petrovic [85] Hypericum rochelt Griseb

and Schenk [85]
'Hypericum humifusum L. [SS] tHypericum sampsonii Hance [39]

Hypertcum maculatum Crantz [84]

Hypericum rocheli Griseb. and

Schenk. [SS] (122) R,.=R,=H; 1.3.6.7-Tetrahvdroxv-
Hypericum rumeltacum Boiss [84]
0-alucosvlxanthone
Hypertcum sampsonii Hance [39]
Garctnta mangos.tana L. [46]

(123) 1.6.7-Trihvdroxvxanthone-
7-0-alvcoside

Platonta CnsignCs Mart. [29]

(Gly: unidentified sugar)

which can be prepared from cambogm, was assigned the

structure of the enantlomer of xanthochymol with a
OH
shlfted double bond [ 1061.
Two related pigments, namely garcinol and isogarcinol
were isolated from Garc~ma indica [107] Garcinol was
OMe
f” assigned the structure of cambogmol(145), however, their
UV spectra m ethanol differed significantly, and It was
Me0
suggested that camboginol lacked the extended con-
Jugatlon m the cyclohexane rmg. The UV spectrum of
cambogmol was repeated m cyclohexane and shown to be
HO
compatible with the orlgmally proposed structure. A
OMe solvent-dependent UV spectrum had already been noted
for xanthochymol [lOS] Ultimately, the X-ray crystal
129 structure of lsogarcmol mdlcated Its Identity with cam-
0
bogm (147), and the formation of lsogarcmol from gar-
cinol, as well as physlcal data, suggest that the latter is
OMe
ldentlcal to cambogmol (145) [ 11 I]
Ad’ ffie~conn I24
) ( + CIS.luelconn ) A related compound, nemorosonol, isolated from the
C6Hb fruits of CIusu~ nemorosa has been assigned the tncyclode-
OH
cane structure (148). It IS suggested that the various
OH polylsoprenylated benzophenones may orlginate from a
common precursor (150, R = prenyl or 2+sopropenylhex-

I30
HOTO\, 4-enyl) by cyclizatlon between C-l and C-6 to form the
bicychc compounds and C-10-C-l and C-6-C-7 to form
148.
Sarothrahn (149) from Hypericum Japomcum has antI-
6Me mlcroblal properties, and IS closely related to other
131 fihcmic acid derivatives (which lack a benzoyl group)
Scheme 4 found m this and other Hyperxum species. Three other
984 G J BENNETTand H-H LEF

Table 13 Xanthonohgnolds

(124) Ri=H. R,=H. R,=H. R+=Me. (126) RI=OH. Rz=OMe. RzJ=H. R+=Me,

Kielcorin Candensin C

Hypericum androsaeaum L C34.881 Hypericum canariensLs L [24]

Hypericum calycinum L II=31 *vlsrnla guaram~rangae Huber [28]

Hyperrcum canar~ens~s L c241

Hyperrcum ericotdes L [SQ] (127) R,=H. Rz=OMe. Ra=H. Ra=Me.

Hypericum maculatum Crantz [SS] Candensin n 1HvDericorinl

*
Hypericum perforatum L. [ES] HyperLcum canariensis L [24]

Vismla guaramtrangae Huber [ZS] HyperLcum mysorense [90]

(125) Ri=OH. Rz=H. R,=OMes R4=H

Candensin h

Cariapa grandiflora Mart II291

CaraLpa ualor Paula [29]

VLsmia guaramLrangae Hubcr [2S]

(128) Kielcorin B

*Kielmeyera cortacea Mart. [91]

prenylated benzophenones (bromanone, cluslanone, and
marupone) were mentloned m the earher review Cl].
Fmally, one other compound of interest is hermionic
acid. Orlgmally Isolated from Garcznta hermonit, and
assigned a dlphenyl structure [l], it has now been re-
Isolated from G. quaeszta, and on the basis of Its conver-
slon to a xanthone and 13C NMR evidence, Its structure
has been revised to the diphenylether (149) [113]. Decar-
boxylated hermlonic acid (150) and its demethyl denva-
tive (IS), named quaesltol were also isolated [114].
 Xanthones from Guttlferae 985

Table 14 Benzophenones

2.3’-Dihydroxv-4.6-dimethoxvbenzor&?mone

ALlanbLachCa floribunda Oliv. [93]

Garctnta xanthochyaus Hook. f [30]

Symphonta globultfera L. [94]

HOtiH (135) 2.3’.4.5’.6-Pentahvdroxvbenzoohenone

Carctnta pedunculata Roxb. [95]

Biogenetically, these compounds appear to be very close-
ly related to xanthones.
CHEMOTAXONOMY
Recent reviews have outlined the principles of chemo-
taxonomy and the taxonomic importance of various
classes of secondary metabolites [115-1171. As xan-
thones occur widely m only a few, unrelated families of
higher plants, their potential taxonomic value is restricted
to within these few families. This sectlon will examme the
dlstributlon of xanthones within the Guttiferae.
The oxygenation pattern is the most vanable structural
feature of Guttiferae xanthones, and almost forty differ-
ent patterns are known. The major oxygenation patterns
are shown at the top of Table 16, grouped mainly
according to B-ring oxygenation. The number of species
m which xanthones with each oxygenation pattern occur
1s gtven for various subdivisions of the family (cf Table 1).
It can be seen from Table 16 that the varlatlon of
xanthone oxygenation pattern is of some systematic
significance. Some oxygenation patterns appear through-
out the family, while others are restricted to certain plant
groups. Clearly, the first three of the six subfamilies each
produce xanthones with a different range of oxygenation
patterns, suggesting that there are different biogenetic
constramts on the species of each group. A similar or
somewhat narrower range of oxygenation patterns is
shown by the tribes or genera of each of these subfamllies.
This overall picture may become clearer as more plants
are studied.
A species from a particular genus generally does not
contain the whole range of oxygenated xanthones found
in the genus. Some species appear not to synthesize
xanthones, e.g. Calophyllum macrocarpum. This plant
accumulates a C,J, compound, 3,4_dihydroxybenzalde-
hyde, perhaps, it is suggested, due to the absence of a key
enzyme [SS]. Slmllarly, some species appear to produce
only benzophenones, or only simple rather than pre-
nylated xanthones
At first sight, such wide variations within a genus may
appear to suggest that xanthones are of little taxonomlc
value at this level; however, when considered with other
taxonomlc characters, xanthones may be useful in aiding
infra-genenc classifications. For example, closely related
species of Calophyllum have many xanthones m common.
The xanthone distribution within each subfamily will
now be examined in more detad. Besides xanthones, the
Guttiferae contain a wide variety of other metabolites
many of which are also of taxonomlc value and these will
be mentloned briefly.
Kielmeyerordeae
The species of this South American subfamdy are
characterized by an abundance of simple oxygenated
xanthones The two tribes, Kielmeyereae and Caraipeae,
show rune oxygenation patterns m common (Table 16).
Several rather umque patterns containing 7,8-oxy-
genatlon are evident, and interestingly, xanthones with
6,7-dloxygenated B-rings have not been found. Simple
1,3,5_trioxygenated xanthones are common only in this
subfamily, and perhaps related to this 1s the rare occur-
rence of prenylated xanthones. Prenylation is absent in
the Caraipeae tribe, but three prenylated xanthones have
been found in species of the Kielmeyereae tribe. Two of
986 G J BENNFTTand H-H LEE

these xanthones are very cominon III Culophyllum species. meyeroldeae [31], and have led one taxonomist to sub-
A further difference between the two tribes IS that merge the Bonnetlaceae into this subfamily [13].
xanthones without l-oxygenation are common only m
the Klelmeyereae tribe Slmllarly, xanthonohgnolds,
which otherwlse only occur m the Hyperlcoldeae sub-
family, are 5,6,7-trloxygenated m Kzelmeyern species but In Table 16 this subfamdy has been divided mto two
1,5,6,7_tetraoxgenated m Cararpu speclea. groups: Calophyllum and MesualMammea. Both groups
Remarkably. the two genera of the Caralpeae tribe, so contam a similar range of simple xanthones, and show the
far have no oxygenation patterns m common (Carazpa: same common oxygenation patterns (1,5-, 1,7- and 1,5,6-),
7-, 1,3,7-, 1,5,6,7-, 5,6,7- and 1,6,7&oxygenatlon, and but there IS a clear dlstmctlon, m that the latter group
Haploclathra: 1,7-, 1,3,5-, 1,3,5,6-. 1,3,7,8- and 1,7,8-oxy- shows an almost total absence of prenylated xanthones.
genation). Only two are known from a species of Knyea (= Mesuu)
For a long time a morphologtcal hnk has been recog- Cl1
nised between the Klelmeyeroldeae and the family Bon- The 180 species of Calophyllum are found mainly from
netiaceae (Bonnetlo and Archytaea genera), and Hutchm- India to New Gumea [120] The genus appears to be the
son has even grouped the two together as a single family most homogeneous m the famtly as far as xanthone
[ 1181. However, the Bonnetlaceae have also been classl- dlstrlbutlon IS concerned. Almost all the 21 xanthonc-
fied as a tribe m Theaceae [119], a related family m which containing species show both simple and prenylated
xanthones have not been found The xanthones that have xanthones Jacareubin (81) occurs m 17 of these species
recently been isolated from two Bonnetlaceae species (and with 6-deoxyjacareubm (56) m 1l), and IS therefore
show the characterlstlc oxldatlon patterns of the Keel- classed as a taxonomlc marker for the genus [ 1211 This

Table 15 Prenylated benzophenones

(136) R, = H. Rz = Me. Vismiaphenone A

*Vtsmia decrpLens Schlecht-Cham [96]

itsaia guara~~~rrangae Huber [ZS]

(137) R, = Me. R, = H; VismiaDhenone C

*Vismta guaramirangae Huber [28]

0 OH

(138) Vismiaphenone B

Clusia elLLpttctfoltn Cuatr. [97]

*Vtsmta decipfens Schlecht-Cham [96]

(139) IsovismiaDhenone B

Clusia eLlipticiFolLn Cuatr. [97]

H
*Vtsnia decipLens Schlecht-Cham [96]

0 OH

(140) *Clus~a elLtptLcLfoZia Cuatr. [97]

 Xanthones from Guttlferae 987

Table 15 Contrnued

(141) TovoDhenone c

*Tovoa~ta mangle C.Maritz [loll

(142) Tovonhenone B

*Touomita mangle G.Maritz [loll

dH

(144) R = 3-Methylbut-3-enyl (145) R = 3-Methylbut-2-enyl

Xanthochvmol “enantiomer” of 144

Garcinta mannii Ollv. [lo33 CamboeinollGarcinoll

Garcinla ovalifolla Oliv C691 *Garcinta cambogta Desr.[106.108]

Garcinia polyantha 011~. [72) Garctnla hulllensrs [109]

Garctnta staudii Engl. [62] Garcinia indica Choisy [107.111(

Garctnia xishuanbannanensis
Y H.Ll Cl043
Rheedta madrunno (HBK)
Pl and Tr [105]
988 G J BENNETTand H-H LEE

Table 15 Contrnued
-

(146) Isoxanthochymol (147) Enantlomer of 146

GarcLnia ouelifolia Oliv [‘=I Camboain(Isoearcino1)

Garcinia polyantha 011~ 1721 *Carctnia cambogla Desr [lOS]

Garcrnia xLs.huanbannanensLs Garclnra lndtca Choosy [107.111j

Y H LI [104]

(148) Nemorosonol

Clusla nemorosa G F.W Meyer [llO]

OH 0

Saro thral in

Hyperrcum Japonicum Thunb cl=1

umformtty may be a reflectron of the rather narrow In a recent revtew of the genus [120], Stevens equated
geographtc range, and close relattonshtp of many of the C. zeylanrcum (now C lankaensd [21]) wtth C. trapezfol-
spectes mvesttgated Iurn. They do in fact have seven xanthones m common,
Interestmgly, the xanthone content of Calophyllum and only differ in that they each produce two xanthones
spectes often vartes greatly wtth the part of the plant. For not found m the other [2 1, 1221 A posstble geographtcal
example, the three xanthones found m the bark of C vartatton IS suggested m C. walkerr [65] A plant from
zeylamcum, were not found in the umber, whtch contam- Indta yielded four xanthones that were not found m the
ed seven other xanthones [Zl] Thts phenomenon, as well Srt Lankan plant of the same name, however, the bark of
as the structural slmtlartttes of many of the xanthones, the latter was not thoroughly mvesttgated [123] Stgnifi-
makes the chemtcal compartson of Calophyllum spectes cant dtfferences have also been found m two vartettes of
dtfficult C calahu [63,64, 1241
 Table 16. The &stributlon* of simple and alkylated xanthones and related metabohtes in the Guttiferae

Oxygenation patterns
-
Simple xanthones Alkylated xanthones

Sub/amrly/Trrbef’ 57 11 1 1 1 1 15 1 1 61 51 17 1 Othersj 1 1 1 1 Other4 XGII XU WI

(No of species) 5 7 32 33 56 36 75 63 78 6 3 3 3 3
53 75 6 67 6 77 8 7 5 7 5 6
5 6 7 7 8 8 6 7

Kielmeyereae (9) 5 4 6 1 1 61 33 1 12378 3 3 1 3

Caralpeae (7) 1 2 2 1 1 4 12 2 1 3
{Bonnelraceae (2) 1 1 1)

Calophyllum (21) 23 8 14 2 1 1 11 1 1 1 2 1 12378 14 14 18 24, 15

Mesua, Mammea (10) 34 7 6 21 13 5 1 21 2 1 37, 13567 1 1235

Clusieae (10) 1 1 1 1 1345, 345? [38] 4 156

Garcvna (29) 5 5 1 1 3 5 1 125, 1245,

1256, 1347,
1357 2 2 8n 5 1358 1 12 8
3
1 167 2 0
Rheedla etc (6) 3 2 1 1 2 3 2 3
5
r
Moronoboldeae (4) 2 1 1 1 1 1 2 2 1 125, 1256 1 2 2

Lorostemoldeae (2) 2

Cratoxyleae (2) 1 1567 1

Hyperlceae (18) 4 4 1 1 21 3 1 3 25,235, 2567 1 3 235. 367 9 7 1

Vlsmieae (5) 1 2 1 2 1 147, 158, 5678, 1 1 13567 1 2

15678

*Numbers m Table refer to number of species m which xanthones with the particular oxygenation have been found.
IGenera m which several plants have been examined are separated from the rest of the subfannly or tribe (cf Table 1)
$These mmor oxygenation patterns, apart from one, have been found m one species; 2,5-dloxygenatlon found m two species
§1,5-Dloxygenatlon and 1,6,7-tnoxygenatlon found m eight and two species respectively, remainder found in one species
JIXG, xanthone glycosides, XL, xanthohgnolds, BZ, simple and prenylated benzophenones
IIncludes three species which contam xanthones with reduced B-ring
990 G J BENNETT and H-H LEE

Neoflavonotds (and other 4-substttuted coumarms) followmg evtdence supports such a relattonshtp Preny-
and chromones occur m many CalophyUum spectes lated xanthones, have been found m all three tribes of the
[125,126]. Hypertcotdeae, and although they have unique struc-
tures, they are stmtlar to those found m other subfamrhes
(e g 63,80) The presence of xanthones with 7,8- and
Clusrodeae
5,6,7-oxygenation and xanthonohgnotds shows a link
Generally xanthones occur less frequently m the Clus- wtth the Ktelmeyerotdeae subfamtly, and two benzophen-
rodeae than m the precedmg subfamthes, and the range of ones (138, 139) from Vlsmra dwrpwns also occur in a
major oxygenatton patterns IS rather restncted. Xan- specres of Clusra
thones m wfuch I-oxygenatton IS absent are not known, LJnhke the rest ofthe family, the Hypertcordeae contam
but several umque oxygenatton patterns contammg 2- C-glucosylxanthones. They have been found m several
and 4-oxygenatton occur Spectes of both trtbes produce species of Hyperlcum [84,85] and Cratovylum prunifol-
prenylated benzophenones, often as the maJor metab- rum [130], and occur wrth both sample and prenylated
ohtes, but otherwtse the tribes show little m common. xanthones, as well as flavonotds As rt appears that these
In the Clusreae tribe. xanthones and benzophenones glycostdes may be btogenetrcally dtfferent from the xan-
occur in Tuuomztu spectes, but the large, poorly-studted thones rn the rest of the family (see Btosynthests), their
Clusla genus has so far not yrelded any xanthones. presence should not be regarded as evtdence of ‘xan-
Recently, Delle Monache and co-workers have begun to thones’ to support the mcluston of the subfamtly m the
study a number of C’lusra species [ 1 lo] Guttiferae Interestmgly. sample xanthones wrth 6,7-oxy-
The Garcmeae trtbe IS drvrded mto two groups in ‘Table genated B-rmgs are unusually common m Hyperlcum
16 Gmcma and RiieedS~a/Pentaphakmyrnum/Alrcln- species They occur wtth the stmtiarfy substnuted gly-
hlackza. The tribe appears fatrly homogeneous, wtth each costdes and may be bmgenettcally related
group showmg a stmrlar range of sample and prenylated A chemotaxonomtc survey of the Hyperrcum genus has
xanthones recently appeared Cl3 11 In addttton to xanthones, many
Xanthones have been found m about half the Garcmzu flavonords and other phloroglucmol dertvattves have
species studted Btffavonotds occur m almost aIf species been found Vismur species produce prenylated anthra-
and benzophenones m 11 Waterman and co-workers nords and other anthracene dertvattves (vtsmlones) [ 1321
have systematically exammed several Garcmra spectes Stmrlar metabohtes also occur m Psorospermum species
from troprcal Afrrca The subsequent chemotaxonomrc CL331
revrew of the genus shows that m certam cases xanthone
structure correlates well with the mfra-genertc class&
BIOSYNTHESIS
catron [ 127)
Three species from the sectron Rheedropsrs of the genus The charactertstrc oxygenatron patterns of xanthones
have been Investigated, and each contams prenylated from htgher plants were recogmsed early on as bemg due
xanthones wrth 1,3,.5,6-tetraoxygenation as well as xan- to a mtxed shtkrmate-acetate btogenests [53 Along these
thochymol(l44) The benzophenones cambogm (147) and lmes vartous biosynthetrc pathways were proposed
cambogmol(l45) occur m two species from the Gamogm [7,8, IO] and these have been reviewed [l J
section, and the two species which produce gambogrc Early btosynthetrc studies were hmtted to the 1,3,7-
actd (118)and other xanthones with reduced B-rmgs are trtoxygenated xanthones of Gentlana luteu (Genttana-
from the sectron Hebradendron X-Geranylated xan- ceae) [134, 1351 The results Indicated that the xanthone
thones are only known m three Garcwa species, two of nucleus was formed from acetate (rmg A) and a C,C, umt
which belong to sectton Oxycarpus It has been suggested derived from phenylalanme The partrctpatton of an
that the thud spectes, whtch has so far not been asstgned mtermedtate benzophenone (152) was demonstrated by
to a sectron, may also go here [72] Such correlations the mcorporatton of trttrated 152 [135]
were not found m many other secttons, but as only 10% The first study on the btosynthesrs of xanthones m the
of Garczmu spectes have been studred tt IS perhaps too Gutttferae has recently been reported [136] Cmnamtc
early to tell acid, benzotc actd, m-hydroxybenzotc actd and the ben-
Also of interest IS the apparent geographtcal varlatton zophenone (152) as well as malomc acid were effictent
of tetraoxygendtton patterns [ 1271 African Garcmm spe- precursors to mangostm (153) m Garcmla mangosrana,
cues contam 1,3,5,6- (and no 1,3,6,7-) tetraoxygenated tmplymg the pathway depicted m Scheme 5
xanthones, whereas Astan species, apart from one, show Furthermore, the labelled benzophenone (152) was
only 1,3,6,7-tetraoxygenatton. Some xanthones from Afrr- stgmficantly mcorpordted into 8-desoxygartamn (67) and
can Garczmu also occur m species of the related South gartanm (79, R, =H, R, =prenyl) m the same plant
American genus, Kheedla. whtch so far has also yielded These findmgs, coupled wtth the earher studies on Gcn-
only 1,3,5,6-tetraoxygenated xanthones trana lutea, Indicate the mvolvement of benzophenone
The Moronbordeae subfamtly IS rather small, and the 152 m the btosynthests of xanthones with four different
four mvesttgattons so far have produced xanthones srmt- oxygenatton patterns (1,3,5-. 1.3,7-, 1,3,6,7- and 1,3,5,8-k
lar to those m the Clusrodeae The Lorostemotdeae sub- and suggest that tt may be an mtertnedtate m the bto-
family contains only two species from which one preny- synthesis of most higher plant xanthonrs
lated xanthone has been Isolated The proposed drrect m-hydroxylatton of benzoate
(Scheme 5) was suggested, m part, by the poor mcorpor-
atron of p-substrtuted precursors Earlter btosynthettc
Hyperrcoldeae
proposals, such as the choice of maclurm (134) as a
Thts subfamtly of three tribes IS closely related to the umversal xanthone precursor [IO] and the Idea of spuo-
rest of the Gutttferae [ 128, 1291, although tt IS somettmes dteneone intermediates [7], were formulated wrth the
classed as a separate famtly, the Hypencaceae [IZJ The assumptton that shrkrmate derrvatrves were necessartfy
 Xanthones from Guttlferae 991

AI

1% R’ = CO,H, R2 = Me
151b R’ = H, R2 = Me
151C R’ = RZ = H

3x
Malonyl CoA

OH

153 152
Scheme 5.

oxygenated in the p-posltion. As It now appears that
xanthone blosynthesls may not involve such slnkimate
derivatives, the earlier proposals require re-evaluation.
Of the various modes of xanthone formatlon proposed
to date, phenol oxldative coupling [137, 138-J can most
neatly account for the large variety and co-occurrence of
oxgenated xanthones [S] Carpenter et al, postulated the
oxidative coupling of a series of suitably hydroxylated
benzophenones to account for the major xanthone oxy-
genation patterns [8]. This suggestion is compatible with
the new biosynthetic results, as the benzophenones all
require the meta- or 3’-oxygenation for oxidative coup-
ling, and may be derived from benzophenone 152. For
example, the oxidatlve coupling of 152 can give 1,3,5- and
1,3,7-trthydroxyxanthones (Scheme 6, Route A) and
maclunn (134), which may be formed by the 4’-hydroxy-
lation of 152, can produce 1,3,5,6- and 1,3,6,7-tetrahy-
droxyxanthones (Route B)
An alternative to the view that xanthones are formed
from a series of benzophenones, is the proposal of
Rezende and Gottlieb that the xanthone oxygenation
pattern is modified after initial xanthone formation from
a single benzophenone-maclurm (134) [lo]. The ‘pn-
motive’, maclurin-derived 1,3,5,6- and 1,3,6,7-tetraoxy-
genated xanthones could lead to all other oxygenation
patterns by successive nuclear oxidations and/or reduc-
tions. For example, the reduction of the 6-position of
these xanthones would give 1,3,5- and 1,3,7-trioxygenated
xanthones (Scheme 6, Route C).
In view of the recent biosynthetic studies, the 1,3,5- and
1,3,7-trioxygenated xanthones appear more sulted to
occupy the positions of ‘primitive’ xanthones, as they are
clearly more likely to be formed by the direct oxidative
coupling of benzophenone 152 (Scheme 6, Route A), than
by a three-step route via maclurm (134) (Route B + Route
C). The 1,3,5,6- and 1,3,6,7_tetraoxygenated xanthones
may alternatively be formed by the &oxygenation of the
1,3,5- and 1,3,7-tnoxygenated xanthones (Scheme 6,
Route D)
Similar nuclear oxldations/reductlons of the trioxygen-
ated xanthones, can lead to the major oxygenation
patterns of Guttiferae xanthones, as illustrated in Scheme
7 It can be seen that the most common oxygenation
patterns (particularly 1,3,5-, 1,3,7-, 1,7-, 1,5-, and 7-) are
more directly accessible from 152 than from maclurin
(134) in the earlier proposal.
992 G J BENNFTT and H-H LFE

Scheme 6

Benzophenone
152

Oxldatwe couphng
/ \
1,3,5 ( 33 )* 1,3.7 ( 26 )

A i L J i L
1,2,3.5 ( 6 ) 1,s( 29 ) 1,3,5,6( 35 1 1,3.6,7 ( 25 ) I ,7 ( 42 ) 1.3.7,s ( 3 )

14w I/ 01

i,2,5 ( 2 ) 5 (5 ) 1,5,6(22) I ,6.7 ( 7 ) 7( 18) 1.7.8(8)

2SC-2) 1,2,5,6(2) 5,6(2) 1,5,6,7,(7) 6.7(7) 1,6.7,8 ( 4 ) 7,8(4)

5,6,7( 11) 6.78 ( 3 )

*No of species that produce xanthones wth each oxygenation pattern

Scheme 7

The dIscusston so far has centred on the four predoml- always found ortho to an oxygen function 2-Prenylatlon
nant oxygenation patterns of prenylated xanthones, but IS the most common, but is only found m the presence of
avolded the Issue of prenylatlon Prenylatlon IS almost 1,3-dloxygenatlon, suggestmg perhaps that the prenyl
 Xanthones from Guttlferae 993

group mhtbtts reduction of the 3-hydroxyl, which ts very incorporated mto 120, whereas labelled 1,3,6,7_tetrahy-
often absent m simple xanthones droxyxanthone was not, suggesting that the glucosylation
Monoprenylatton occurs less often m the 4-, 8-, or 7- occurs at the maclurm stage, and that both 120 and 121
postttons. A second prenyl group frequently occurs m the are formed by the oxtdative coupling of 3-glucosylmac-
4- or 8-positions 2,4-Diprenylatton IS associated wtth lurm (156)
1,3,5-, 1,3,5,6,- or 1,3,5,8-oxygenatton, but mterestmgly, Interestingly, mangtferin (120) has recently been found
not known wtth 1,3,7- or 1,3,6,7-oxygenation, and 2,8- together wtth 3-C-glucosyhrtflophenone (155) m two
dtprenylation ts hmtted to 1,3,7- and 1,3,6,7-oxygenatton ferns (Hypodematwm) [145], and with the 1,3,7-xanthone
patterns analogue of 155 m Gentiana lactea [146].
As wtth oxygenatton, there 1s little evidence to suggest
whether prenylatton occurs at the benzophenone or
PHARMACOLOGY
xanthone stage, although the latter 1s preferred, e.g. ref
[139] 2-Prenyl-1,3,5-trthydroxyxanthone has been pos- Probably the most important development m thts area
tulated as a precursor to 6-deoxyjacareubin (56) and has been the tdenttfication of the cytotoxtc xanthone
jacareubm (81) [ 1401, a route mvolvmg 6-oxygenation at psorospermm (57) [Sl, 52,541 It shows significant in uwo
the xanthone stage, and m keeping wtth Scheme 7 These acttvtty m P338 leukaemta, colon (C6) and mammary
three xanthones are found together m four Calophyllum (CD) tumobr systems [ 1481. Synthetic studies on psoros-
species. Similarly, 2-prenyl-1,3,7-trihydroxyxanthone permin are m progress [55-573 (see earlier), and anal-
could lead to mangostm (153) vta 6-deoxy-y-mangostm ogues are bemg prepared and tested for simtlar activity
(70). The alternative, that 153 and 70 derive from two [149-J.
benzophenones, 1s less attractive, as it does not mdtcate Mangtferm (120) has been the subject of several studies.
such a close relationship between these co-occurring Anti-mflammatory [lSO], antihepatoxtc [151] and antt-
xanthones It can be seen that a series of modtfications viral (herpes) [ 1521 properties have been reported. Man-
(oxygenation, further prenylation, cyclizatton etc ) to the gtferm has also been shown to cause the in ultra activation
two basic 2-prenylxanthones can produce over 40, or of the lymphocytes of tumour-bearing rats [153].
about half of the known prenylated xanthones. In contrast to mangtferm (120), which is reported to be
It had been suggested that mangiferm (120) was bio- a CNS sttmulant [ 1541, mangostin (153) and several of tts
genettcally related to flavonotds [S, 1411, due to its dertvatives [155] as well as xanthones from Calophyllum
occurrence m some plants m the presence, or apparently mophyllum and Mesua ferrea [ 1561 produce CNS depres-
in place of C-glucosylflavones [142], rather than with sion in rats and mice. Many of these xanthones, especially
other xanthones Pujita and Inoue have conducted a mangostin, exhibit significant anti-inflammatory proper-
thorough study on the biosynthesis of mangtferm (120) ttes at doses of 50 mg/kg [155,156]. They have no
and tsomangtferin (121) m Anemarrhena asphodeloides analgestc or anttpyrettc effect, but mangostm shows antt-
(Ltliaceae) [143, 1441. The results mdtcate that the xan- ulcer acttvtty The interference of mangostm with inflam-
thone nucleus 1s mdeed formed from a flavonotd-type matory and tmmunopathologtcal responses has been
C,C, precursor (p-hydroxycinnamate) coupled with two further studted [ 1571. The synthetic 3,6-dt-O-glucosyl-
malonates (Scheme 8) The labelled benzophenones, tri- mangostm produces myocardial sttmulatton and a rise in
flophenone (154) and maclurm (134) were significantly blood pressure m dogs [ 155, 1581.

fy-ycooH 2x
c
Malonyl CoA OH
“ON

CI ) 3’. oxldatlon
(II ) 3 glucosylation

2.6’&4-6’
120 & 121 *
Oxldative
couphng

156

Scheme 8
994 C J BF~NFTT and H-H LEF

More xanthones have been tested for zn cltrn mhlbrtlon tlon between 13C NMK chemical shifts of C-4b and C-7
ofmonoamme oxldases (MAO’s) [159] Two compounds, of various 1,3-oxygenated xanthones and tuberculosis
I-hydroxy-3,8-dlmethoxyxanthone and 1,3-dlhydroxy- mhlbltlon [ 1651. Three potent xanthones were Identified,
7,&dimethoxyxanthone (swertmm) were Identified as the of which gentlsem (31) was the most active
most effective mhlbltors of type A MAO. but were weak
type B MAO inhlbltors In another study 1,5,8-
C0NCL.I SIOY
tnhydroxy-3-methoxyxanthone also showed selective
type A mhibltlon [146] A number of xanthones also In conclusion, the Guttlferae produce a wide variety of
mhlblt xanthme oxldase [160] 1,3,6,7_Tetrahydroxyxan- both simple and prenylated xanthones The growmg
thone was the most potent of the compounds tested Interest in thesecompounds IS shown by the large number
Several prenylated xanthones possess significant an- Isolated durmg the last eight years An attempt has been
timlcrobiafproperties Mangostln shows broad-spectrum made in this review to correl&e xanthone structure with
antibacterraf activity, mcl’udihg the inhibition ot”penic& the ciasslcar taxonomic divisions ot-the Ciluttiterae. The
hn-resistant strams of Staphylococcus uweus, as well as new results on xanthone biosynthesis support the Idea of
antifungal propertles [161; lhZ] Xanthones from Culn- a common_ benimphermne precursor_ ahh<zugh forth!%
phybn mophyllum, particularly 6-deoxyjacareubm (56) studies are stilt required Lastly, the pharmacology of
andjacareubm (81) [163], and the benzophenoncs kolan- xanthones has been summarlred, mdicatmg their poten-
one (143) [102] and garcmol (145) [109] also exhibit teal as medlcmal agents
antJmJCJ’Obla~ propertles
A tuberculostatlc effect has been noted m many natural A(XnoM.lrdqementc---The authors are grateful to Dr G M
and synthetic xanthones [I 641. A quantltatrve structure- Kltanov for his commumcatlons, and one of us (GJB) thanks the
actlvlty relatlonshlp (QSAR) study has found a correla- NatIonal IJnrverslty of Slngdpore for the awdrd of a scholarship

APPENDIX

SpecIea-compound Index

Xanthones except (rrrrl)-xanthollgnold, ( [-glycoslde ( \-benzophenone

(132), (133)
51
4,l 21
71
71~ 73
70, 75
74, 76-78
117
1, 3 4, 18, 56, 73, 81, 116

28, 36. (125)

2.36 -
36, (125)
(13CGO)
(148)
48. jl20}, (JZI)
(145) (147)
88
118, 119
(145)
4, (145), (147)
(143)
48. 52. 54. 55, 68, 70, 73, 74. 79. 96-104 108. jl22).
(134)
(144)
109
86, (144), (146)
(135)
90. (144), (146)
112~114
69
[IS1 a *]
88. (144)
39
3, 4. 12, 14, 15. 30, (134)
(l44), (146)
 Xanthones from Gutttferae 995

APPENDIX Contmued

Haploclathra lreantha (Benth.) Benth 15, 21,35,38,42,45,46,49

H panrculata (Mart) Benth 7, 15, 21, 23, 25, 29, 31, 33, 38, 40, 41
H vertrcrllata Ducke 4, 7
Hyper~cum androsaemum L 10, 11, 27, 47, 48, SO, 80, 82, (124)
-
H aucherl Jaub et Sprach 48, {120)
H balearuxm L 1, 4, 11
H barbatum Jack (1201
H bolsslerl Petrovic {lZOl> (1211
H calycmum L (124)
H canartensts L 1, 5, 10, 26, 37, 63, (124),
--- (126), (127)
H. degenu Bornm 31
H errcoldes L 1, 4, 34, 43, (124)
H hvsutum {121} -
H hum&urn L (1201
H. Japomcum Thunb (149)
H maculatum Crantz 115, {120}, (124)
H mysorense 1, 2, 4, 6, 7, 924, (127)
-
H perforatum L (124)
-
H rocheh Grlseb and Schenk (1201, {121}
H rumehacum Botss 11201
H sampsonu Hance 26,64,82, { 120}, { 121)
Klelmeyera corlacea Mart. (128)
-
K rublflora Camb 26
K speclosa St Hill 26
Mahurea tomentosa Ducke 4, 7
Mesua ferrea L 42
Platoma msrgms Mart. 32, { 123)
Psorospermum febrlfugum Sprach 11,44,53,5741
Rheedla benthamtana PI and Tr 86,88,89,91
R. brasdlensls (Mart ) PI and Tr 62,67, 8694
R gardnerlana PI and Tr 62, 67, 84, 8691
R madrunno (HBK) PI (144)
Symphoma globullfera L (134)
Touomlta brasllrensls Walp 36
T excelsa Andrade-Ltma & G Marttz 16, 18, 20, 22
T mangle G Marttz 95, (141), (142)
Vlsmra declplens Schlect-Cham (136), (MU, (139)
V guaramvangae Hubcr 1, 2, 4, 7, 8, 11, 13, 15, 17, 19, (1%126),
-- (136), (137)
V aumeensts (L ) Chotsv 83,85, 110, 111

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