Renewed Studies on Some Lichen Metabolites and Their Development

9 Pages·1992·0.49 MB·English

by  Shoji Shibata

植物研究雑誌
J. Jpn. Bot.
67: 63-71 (1992)
Review
Renewed Studies on Some Lichen Metabolites
and Their Development
Sh吋iSHIBATA
Shibata Laboratory of Natural Medicinal Materials，
c/o Minophagen Pharrnaceutical Co.，3 rd Tornizawa Bldg.，
3・2-7Yotsuya，S hinjuku・ku，Tokyo，1 60 JAPAN
過去の地衣成分研究の再検討とその新しい展開
柴田承二
柴田天然薬物研究室 160東京都新宿区四谷 3-2-7第三富沢ピル4F
(Received on November 9，1 991)
In response to the criticisrns by the rnodern concepts，re newed investigations have been perforrned
on sorne lichen substances studied earlier by the author. The original structures of psorornic acid and
didymic acid were reconfirrned by the present knowledge and the rnethods currently used. Retigeranic
acid was separated by HPLC into two stereoisorners，A a nd B，w hose structures were established by
X-ray crystal1ography. As an ew developrnent of earlier study，a n antiviral agent against human
irnrnunodeficiency virus (HIV-l)，GE -3S，was induced from ah ost-rnediated anti-turnour active lichen
・
polysaccharide，G E-3.
Since Professor Asahina and 1 published (Shibata 1965). In earlier investigations of lichen
“Chemistry of Lichen Substances" in 1954，i n substances，cl assical chemical methods were mostly
which about 75 lichen substances with established employed，a nd modern spectroscopic analysis and
chemical structutes were recorded (Asah泊aand chromatographical techniques have been intro-
Shibata 1954)，se veral review articles have been duced into this field only after t~e World War II.
published to follow the progress of studies on Myc oworkers and 1a pplied NMRs pectrometric
lichen metabolites (Culberson 1969，Hu neck 1973， analysis at first in 1960s to elucidate structural
Elix，W hitton and Sargent 1984). The latest review correlation of usnic acid，is ousnicacid and their
・
of Elix et al. includes about 346 lichen metabolites. dihydroderivatives (Shibata et al. 1962，S hibata
Meanwhile，1p roposed ab iogenetical systematiza- and Taguchi 1967). Thereafter，th e general appli伺ー
tion of lichen substances to elucidate their tion of IR，N MRa nd Mass spectrometry to the
structural correlation on the basis of biosynthetical structural elucidation of lichen metabolites was
schemes classified into acetate-malonate，s hiki- reviewed (Shibata 1978). Recently，o ur earlier
mate，m evalonate and amino acids pathways works of some lichen metabolites have been
-63ー
64 植物研究雑誌第67巻第2号 平成4年4月
criticized sometimes in view of the modern
concepts. Then appropriate response should be
given reexamining the earlier results by the present
knowledge and the methods currently employed.
HO
ln this article 1w ould like to give some examples
of renewed studies on the lichen substances on
which 1h ad once been engaged. explain the formation of the phthalic anhydride
Psoromic acid -ln 1939 Prof. Asahina and 1 derivative on pyrolysis (Dean 1963).
reported revised structure of psoromic acid，a But in 1976 Huneck and Sargent reconfirmed
depsidone isolated from Alectoria sulcata，o n the our structure of psoromic acid by由espectroscopic
basis of the formation ofaxanthone derivative data and degradation reactions in which aS miles
from ad iphenyl ether carboxylic acid derivative rearrangement was involved by the methanolysis
derived from hypopsoromic acid (Asahina and of methyl 0 ethylpsoromate.
・叩
Shibata 1939). Psoromic acid had been represented They assumed the intermediate formation of grisan
earlier as af ormula having carboxyl at the ortho- on the pyrolysis of psoromic acid.
position of depside linkage by reason of the Sala and Sargent (1979) synthesized psoromic
formation of phthalic anhydride on pyrolysis. The acid by af ew steps of selective functionalization
revised formula explained this by the classical salol reactions to reconfirm the structure synthetically.
rearrangement. Didymic acid -The structure of didymic acid
Later，D ean proposed an alternative structure isolated from Cladonia pseudodidyma， Cl.
of grisadienedione type for psoromic acid to floerkeana，v ar. suboceanica，C l. bacillaris var.
伊3
Hにハ~OCH3 OCH3
Y r
OC'"γF RO 、0'" CH3
CHO I 一1 じH3 t OR
0- CO
。
J~aNH2
列 CH.，曹
i
介
OCH3t23? r(cid:631)OCH3
H3eo OH Br'Y'C H3 C....\u04 nRv O'y~ ~-- V~ ......... ず"， ""CH3
J CH3 OCH3 - CH3 OR
April 1992 Journal of Japanese Botany Vol. 67 No. 2 65
CHO CH3
pacifica and Cl. incrassata wぉ putforward in 1944 Onc ontrolled oxidation of didymic acid methyl
by the following chemical reactions (Shibata 1944): ether with KMn04 in pyridine，th e formation of
The carbonskeleton and the disposition of orthodicarboxylic acid derivative was assumed
佃
alkyl(n幽C3H7and n-C5H1 1) groups in didymic acid to support the positions of C5H11 and COOH
molecule were determined by the derivation from groups.
synthesized 1，9-dimethyldibenzofuran. The special In 1983 Sargent attempted to synthesize didymic
correlation between COOH and OHg roups was acid and proposed an altemative formula having
proved by the blue coloration with FeC1，a nd the n-CH in l-position and n-CH in 9positionby
3 3 7 5 11 ・
vicinal disposition of nCH11'COOH and OH reason of the different melting point of his
・ 5
was deduced from ac haracteristic behaviour of synthesized product with the data which 1r eported
didymic acid forming three layers at the extraction earlier for natural didymic acid.
from the ethereal solution with aq. NaHC0 Because of shortage of the material，1 c ould not
3・
.
H3CO 'OR RO OR'
I
R=H Didymic acid u_" _ r R=CH3 R' =H
1KV 'Mn04 i.! _n p__y__r_. K.._M_ ω_ 4i• n lR=R'zCH3
ム pyr.
C3H7ψCOOR C~~O_.O_H..'" C__O_O_H_， J
.t"".z ...
COOR
H3CO OCH3 RO OR'
R=H or CH3 R=R'=CH3
KMnOA
pyr. -
RO
66 植物研究雑誌第67巻第2号 平成4年4月
effectively response to his demand for direct com- mentary analysis of methyl ester of the controlled
parison of natural and synthetic didymic acid. IR， oxidation product (Obs. C 65.51，H 6.08) are
lH NMRa nd 13C NMRs pectral analysis，w hich adopted within the error to either the new，
had not been used for didymic acid in earlier days， C24H2608，o r the earlier molecular formula，
are not effective for the determination of alter- C21H2207 (Anal calcd. C 65.28，H 5.70).
native disposition of two alkyl groups on the Retigeranic Acid -Myc oworkers and 1p ro-
dibenzofuran ring. Mass spectral analysis，w hich posed in 1972 (Kaneda，T akahashi，Ii taka d
組
seemed to give ac onclusive evidence，ha s not been Shibata 1972) an ovel sesterterpene structure for
reliable because of difficulty in electronic cleavage retigeranic acid isolated from Lobaria retigera and
of the dibenzofuran ring. L.おidiosavar. subisidiosa. This structure was
Consequently，1 u sed X-ray crystallography for confirmed by X-ray crystallographic analysis of its
methyl ester of the controlled oxidation product， p-bromoanilide侭釦eda，Iitaka and Shibata 1974).
which was assumed to have an ortho dicarboxylic Recently，C orey and his collaborators (Corey，
acid system. The result given by the collaboration Cesai and Engler 1985) attempted at otal synthesis
of Prof. Y. Iitaka showed that the compound of racemic form of this compound，a nd Paquette
should be formulated as below revising the and his collaborators (Wright，Dr tina，Ro berts and
structure proposed earlier (Shibata and Iitaka Paquette 1988) also tried to perform an enantio
姐
1984). specific total synthesis of the same compound.
In spite of the structural correction of the In response to Prof. Corey's request 1s ent my
oxidation product，t he original didymic acid sample of retigeranic acid，an d soon he found that
structure has been proved to be correct including methyl ester of mys ample showed two peaks on
the disposition of n-CsH II group. Interestingly the HPLC，on e major (r.1. 30 min) and one minor
enough，t he calculated C，H values in the ele- (r.t. 31.2m in)，a nd the minor one was identical
、夕COCOOCH3 C:SH11
d vーーイ/、(cid:631)ベ!:OOCH3
、、
責3CO'" y 、0/~ 'OCH3
民1ethylester of ac ontrolled oxidation
product of methyl O-methyldidymate
X-ray crystallographical data:
Mol formula: C24H2608;
mol. wt.: 442;
Anal calcd. C6 5.15，H 5.92
恥fonoclinic;space group Pz}/n;
z= 4，Dc alcd. =1. 299 gcm-3，
a= 19.522(10)，b= 8.271(4)， Fig. 1. Ap erspective drawing of the molecule of the methyl ester
c= 1 4.153(7)λ;s =97.99(5); V=2263A; of ac ontrolled oxidation product yielded from methyl 0・
νfor CuKα=7.74 cm-1 methyldidymate.
April 1992 Journal of Japanese Botany Vo1. 67 No. 2 67
with methyl ester of his synthesized product. now become clear that we had determined X-ray
1e xamined myo riginal sample of retigeranic crystallographical structure of p-bromoanilide of
acid which gave as ingle spot on TLC，bu t it was the minor component (A) of natural retigeranic
separated inωtwo peaks on HPLC over an ODS acid which might readily crystallize out from the
column. The two components，A and B，g ave mixture solution.
superimposable UVc urves and the sneMass Then X-ray crystallographical analysis of two
田
number. componen臼(Aand B) of natural retigeranic acid
1s ent myo riginal sample of p-bromoanilide of has been performed. The major component (B)，
retigeranic acid，wh ich was used for X-ray analysis， which is now designated retigeranic acid B，m. p.
to Prof. Corey to be identified with that of 'his 220-2220，[ α]D -30.40 (EtOH)，h as been sub-
synthetic retigeranic acid p-bromoanilide. It was jected to X-ray crystallographic analysis to have
HPL-chromatographically identical with p- s-i sopropyl，R at C(18)，a nd the IDinor com-
bromoanilide of his synthetic compound. It has ponent (A)，r etigeranic acid A，m .p. 188-1900，
50も咋
h
CH3CN :、、、
“、 、
、
、、
、
.、、
0.‘4ま'+ 、、、
、
.、、
、.、.
.、
、、、
、
. ‘、
、、胃・・・・・・句・・・・・・・・---ー・ー・・・----、.胃 00も
H3CN
凸
0
ω
20.
4己
m
A
oM B
m
A
4
a
A
。
Y
~、、
.
。
τ ' '
10 20 30 40 50 min
Retention time
Fig.2. High performance liquid chromatogram of native retigeranic acid. Column: ODS; mobile phase: 3070 CHCOOH/
3
CHCN. UV: 253 nm.
3
68 植物研究雑誌第67巻第2号 平成4年4月
H
COOH
Retigeranic acid A Retigeranic acid B
Sa t C R at C
18 18
(minor) (m吋or)
[α]D -86.50 (EtOH)，t o have α-isopropyl retigeranic acid deduced from X-ray analysis of its
again坑 methylgroup at C(15)，S a t C(l8). p-bromoanilide. Paquette and his coworkers
According to Corey's synthetic process starting (Wright，D rina，R oberts and Paquett 1988)
with J5_ 3αisopropyl-9methylhydrinden-6-one， synthesized enantiometrically pure retigeranic acid
・ 圃 ・
江isobvious出athe synthesized retigeranic acid A， A and its stereo-isomers at A/B and B/C ring
the minor partner，w hose stereochemistry was junctures.
previously illustrated in our earlier paper as
Retigeranic acid A Retigeranic acid B
m.p. 188-1900 m.p. 220-2220
αI]D -86.50但tOH) [α]D -30.40 (EtOH)
Fig. 3. The stereochemistry of retigeranic acid A and B.
April 1992 Journal of Japanese Botany Vol. 67 No. 2 69
The biological activity of the lichen polysaccharide， sidered to be the aetiological agent of acquired
GE・3and its sulphate (GE・3・S) immune deficiency syndrome (AIDS)，ha s exten-
It is well known that lichens contain poly- sively been investigated. Several anti-HIV com-
saccharides，h omo-and heteroglycans，in af airly pounds，ri bavirin，ph osphonoformic acid，re com-
high percentage besides lichen metabolites of binant interferon-α，3 '・位ido2'，3にdideoxythy-
嗣
smaller molecular size. midine (AZT) and glycyrrhizin (Ito，N akashima，
Some years ago，m yc oworkers and 1f ound that Baba，Pa uwels，De clereq，Sh igeta and Yamamoto
some s-g lucans in lichens show host-mediated 1987)，ha ve already been tested against AIDS. It
antitumouractivities against implanted Sarcom:;l. has also been noted that heparin and sulphate of
圃
180 and Ehrlich's carcinoma of mice (Shibata et dextran，α(16)glucan，are effective to suppssthe
・ 問
al. 1968，F ukuoka et al. 1968). Especially GE-3， infection and replication of HIV (lto，B aba，Sa to
partially acetylated pustulan，a s(1 -6)-glucan， and Pauwels 1987). It prompted us to study the
isolated from Umbilicaria esculenta (= G yrophora anti-HIV activity of lichen polysaccharides and
esculentα'))，sh owed ac onstant and noticeable anti- their sulphat Recent experimenta1 results showed
， 白.
tumour activity by i.p. administration to ICR mice that sulphated GE-3(GE3S)is the most promising
・・
(Shibata，N ishikawa，T akeda and Tanaka 1968， agent for HIV suppression (Hirabayashi，I wata，
Nishikawa，Ta keda，Sh ibata and Fukuoka 1969). Ito，S higeta，N arui，M ori and 8hibata 1989).
It has been shown recently that the anti-tumour GE・3・S(8 content 13.8070 [α]D -25.00，m ol.
activity of由epolysaccharides would be caused by wt. 200，000) was prepared by sulphonation of
the biological response modifiers induced by an GE-3 using chlorosulphonic acid.
inflammatory change in liver occurring immedi- For testing the anti-HIV activity of GE帽子S，the
ately after i.p. injection of the reagent. HTLV-I carrying cellline，M T-4，a nd the human
民1acroscopica1increase of the liver weight of leukemic T-cell line，Mo lt-4 (clone 8) were used.
mice was observed by i.p. administration of GE-3， The cells were cultured in RPMZ-1640 medium
50 mg/kg/d ，an d temporary increase of leucocytes supplemented with 10% fetal calf serum (FCS) ，
fol lowed by excretion ofαl-acid glycoprotein in 100 IU penicillin G and 100μg/ml streptomycin.
the serum on day 6-9 was shown. By electro The HIV was obtained from the culture super-
圃
foc ussing the mouseαl-acid glycoprotein was natant of the Molt-4/HTLV -111cell line.
お ・
separated 泊intωOα町rAG-1(lliP 3.勾2)and α引r回AG- Anti-viral activity of GE・3・Swas determined by
(οIEP. 3.4)， and α1AG1inhibited in vitro the trypanblue exclusion using ah aematocytometer.
・ ・
growth of L1 210 cells at the concentration of 200 Molt-4 (clone 8) cells were infected with HIV at
∞
μg/ml. Therefore，α1・AG・1may play as ignifi- MOlofO. 2a nd incubated for 1h r at 370C. After
cant role in the host-mediated anti-tumour activity washing，th e infected cells were suspended in a
of GE3.The“ similar biological responses were culture medium. The number of cells was adjusted
・
shown by i.p. ad凶n凶is附t位r副ati∞onぱofliche阻n机an九1，as (1ト-3 to 1X 105c ells/ml，an d the cells were brought into
(ιト1-凶-4)glucω叩1c札an民1，and p叫achym札an払1，a 戸仰(1ト-3勾泌制)g泡胤l山ucc叫a，民n ωtO each well (90 wells microtiter) containing various
mice (何w匂a剖tanabe，Iwai，Sh ibata，T ak泊1ashi，Na rui concentrations of GE・3・S，other lichen poly-
and Tashiro 1986). saccharides and their sulphates. After incubation
Recently，c hemical inhibitors against human at 370Cf or 4d ays in aC O-incubator，ha lf of the
2
immunodeficiency v凶 s但IV)，which is now con- culture medium was exchanged with the fresh
70 植物研究雑誌、第67巻第2号 平成4年4月
medium. After incubation for another 2d ays at References
370C，t he number of viable cells was counted
Asahina Y. und Shibata S. 1939. Untersudungen uber
microscopically by trypanblue exclusion method. Flechtenstoffe 92 Mitteil. Uber Psoromsaure (111
Mitteil). Ber. deutsch. Chem. Ges. 72: 1399-1402.
Only 3X 105c ells/ml of Molt-4 (clone 8) cel1s Asahina Y. and Shibata S. 1954. Chemistry of Lichen
can survive on day 3a fter HIV- infection as com- Substances，Ja pan Soc. Promotion of Science，To kyo.
pared with 10 x1 05c ells of the uninfected control. Coresyyn tEh.e sJi.s ，oCf e s(a:ti ー)恥r1e.tiCg.e raannidc Eancgidl.e rJ . T.A mA.. C19h8e5m. .T oStoac.l
Ont he other hand，in the presence of 35ρg/ml 107: 4339-4341.
Culberson Ch. F. 1969. Chemical and Botanical Guide
ofGE・3-Sthe host cells w町ecompletely protected to Lichen Products，Un iv. North Carolina Press. Chapel
against cytopathic effect of HIV. GE-3-S at this Hi11.
Dean F. M. 1963. Naturally occurring oxygen ring com
・
concentration gave no cytotoxic effect on the host pounds. London Butterworths.
cells. The immunofluorescene (IF) method showed Elix J. A.，W hitton A. A. and Sargent M. V. 1984.
Recent Progress in the Chemistry of Lichen Substances.
that 52.4070 of恥10lt・4(clone 8) cells expressed viral Progress in Chem. Org. Natural Prod. 45: 104-234
antigens on day 3o f HIV- infection，wh ereas in the (Springer Verlag，W ien，N ew York).
Fukuoka F.，N akanishi M.，S hibata S.，N ishikawa Y.，
presence of 31μg/ml of GE-3-S the viral antigen Takeda T. dTanaka M. 1968. Polysaccharides in
加
expression was almost completely suppressed. lichens and fungi. 11. Anti-tumour activities on
sarcoma-180 of the polysaccharide preparations from
GE-3-S at the same concentration completely Gyrophora esculenta Miyoshi，C etraria islandica (L.)
inhibited the formation of giant cells of Molt-4 Ach. var. orientalis Asahina and some other lichens.
Gann 59: 421-432.
(clone 8) induced by the infection of HIV. In com“ Hirabayashi K.，Iw ata S.，It oM .，S higeta S.，Na rui T.，
parison with other lichen polysaccharides and their Mori T. and Shibata S. 1989. Inhibitory effect of a
lichen polysaccharide sulfate，G E-3-S，o n the replica-
sulphate so far examined，G E3Sis the only one
・・ tion of human immunodeficiency virus (HIV) In vitro.
that exhibited anti-HIV activity. Chem. Pharm. Bull. 37: 2410-2412.
Huneck S. 1973. Nature of Lichen Substances. The
The presence of sulphate group in the molecule
Lichens，p p.495-546，Ed . Ahmadjian V. and Ha1eM .
of GE3-Sis essential for the anti-HIV activity， E.，A cademic Press，N ew York，L ondon.
・
Huneck S. and Sargent M. V. 1976. Depsidone synthesis.
since GE-3 is not effective. It has been known that
V. The chemistry of psoromic acid: A reinvestigation.
dex仕組sulphateand heparin are also suppressive Austral. J. Chem. 29: 1059-1067.
ItoM .，Na kashima H.，Ba ba M.，Pa uwels R.，De clereq E.，
against HIV infection. All出esepolysaccharide Shigeta S. and Yamamoto N. 1987. Inhibitory effect
sulphates expressed no inhibitory effect on the cell- of glycyrrhizin on the in vitro infectivity and cytopathic
activity of the human immunodeficiency virus [HIV
free HIV reverse transcriptase activity. Therefore， (HTLV-III/LAV)]. Antiviral Res. 7: 127-137.
these polysaccharide sulphates would interfere the Ito M.，Ba ba M.，Sa to A. and Pauwels R. 1987. Inhibitory
effect of dextran sulfate and heparin on the replication
adsorption of HIV particles to the surface of T-4
of human immunodeficiency virus但IV)in vi tro .
cells，pr obably at the site of the viral envelope gp Antiviral Res. 7: 361-367.
Kaneda M.，Ta kahashi R.，It aka Y. and Shibata S. 1972.
120. Retigeranic acid，a n ovel sesterterpene isolated from the
lichens of Lobαria retigera group. Tetrahedron Letters:
4609-4611.
1w ish to thank Prof. Yoichi Iitaka for his co
・ Kaneda M.，Ii taka Y. and Shibata S. 1974. X-ray studies
operation for X-ray crystallographical analysis. of C25 terpenoids. IV. The crystal structure of
retigeranic acid p-bromoanilide. Acta Cryst. B 30:
Thanks are a1so due to all由ecollaborators，wh ose
358-364.
n但n邸 arecited in the references，fo r persuing the Nishikawa Y.，Ta keda T.，Sh ibata S. and Fukuoka F. 1969.
Polysaccharides in lichens and fungi. 111. Further
works elucidated in this article.
investigation on the structures and the antitumor activity
of the polysaccharides from Gyrophora esculentα
，
Miyoshi and Lasallia papulosa Llano. Chem. Pharm.
April 1992 Journal of Japanese Botany Vo1. 67 No. 2 71
Bul1. 17: 1910-1916. Further studies on the structure of retigeranic acid.
Sala T. and Sargent M. V. 1979. Depsidone synthesis. Chem. Pharm. B叫1.39: 3051-3054.
Part 14. The total synthesis ofpsoromic acid: Isopropyl Watanabe M.，Iw ai K.，Sh ibata S.，T akahashi K.，N arui
ethers as useful phenolic protective groups. J. Chem. T. and Tashiro T. 1986. Purification and characteriza-
Soc. (London)，P erkin Trans I: 2593-2598. tion of mouseαI acid glycoprotein and its possible role
Sargent M. V. 1983. Private Communication，M ay 31. in the antitumour activity of some lichen poly-
Shibata S. 1944. Uber Didymsaure，e inen neuen Typus saccharides. Chem. Pharm. Bull. 34: 2532-2541.
der Flechtenstoffe. Acta Phytochim 14: 9-37. Wright J.，D rtina G. J.，R oberts R. A. and Paquette L.
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H. and Chiang H・C.1962. Decomposition of usnic acid. sesterterpenes. Enantio-selective synthesis of (ー〉
VI. Studies on the ozonolysis products of 0，0 retigeranic acid A. J. Am. Chem. Soc. 110:
・
diacetylusnic acid. Chem. Pharm. B叫1.10: 477-483. 5806-5817.
Shibata S. 1965. Biogenetical and chemotaxonomical
aspects of lichen substances. Festschrift Kurt Mothes 要旨
zum 65 Geburstag，p p.451-465 (Gustav Fischer
Verlag，Je na). 著者らが以前に発表した地衣Alectoriαsulcαtα
Shibata S. and Taguchi H. 1967. Occurrence of isousnic
acid derived from dihydrousnic acid. Tetrahedron 等の成分のpsoromicacid， Cladoniαpseudodid-
Letters: 4867-4871. ymα等の成分didymicacidの構造については近
Shibata S.，N ishikawa Y.，T anaka M.，F ukuoka F. and
年になって異論が提出されたが，何れも新しいス
Nakanishi M. 1968. Antitumour activities of lichen
polysaccharides. Z. Krebsforsch. 71: 102-104. ペクトル分析あるいはX線結晶解析の手法によ
Shibata S.，N ishikawa Y.，T akeda T. and Tanaka恥ι り従来の構造式の正しいことが証明された.また
1968. Polysaccharides in lichens and fungi. I. Anti-
tumour active polysaccharides of Gyrophora esculenta Lobariαretigerα群の特異な sesterterpene，reti-
Miyoshi and Lasallia papulosaμch.) Llano. Chem. geranic acid，は高速液体クロマトグラフによっ
Pharm. Bull. 16: 2362-2369.
てA，B2種の異性体に分離されその各々がlS0-
Shibata S. 1978. Lichen Substances. Methodicum
Chimicum，V o1. 11，Pa rt 3，pp .208-223，Ed . F. Korte propyl基を含むC-18位に於けるSおよびRの立
(Academic Press，N ew York，S an Francisco，Lo ndon. 体異性体であることがX線結晶解析で立証され
G. Thieme Pub ，.l Stuttgart. Maruzen Co.，L td.，
Tokyo). た.また宿主仲介抗腫傷性を示した Umbillicariα
Shibata S. and Iitaka Y. 1984. Renewed studies on the esculentαの地衣多糖体GE-3を硫酸化した GE-3-
structure of didymic acid. Chem. Pharm. B叫1.32:
Sがinvitroで抗HIV活性を示すことが認めら
366-368.
Sugawara H.，K asuya A.，Ii taka Y. and Shibata S. 1991. れた.