Studies On Chemical Constituents Of Ganoderma Sinense And Ganoderma Lucidum

Ganoderma sinense Zhao.Xu et Zhang and Ganoderma lucidum(Leyss.ex Fr.)Karst.are used for treatment of asthma and hypertension in Chinese pharmacopoeia.Lingzhi(Ganoderma)has been used as a folk medicine for thousands of years and is a well-known traditional medicine in China.Ganoderma contains more than 100 species,with wide distribution in China.Recent studies showed that the mushrooms of Ganoderma possess anti-inflammatory,immune regulation,hepatoprotective,antitumor and other pharmacological effects.Previous phytochemical investigations have shown that Ganoderma lucidum produces a large number of compounds,of which triterpenoids are considered to be major constituents.But triterpenoids from Ganoderma sinense have not been reported in literature.To clarify the differences between Ganoderma sinense and Ganoderma lucidum,we investigated the chemical constituents of them.In this thesis,the systematic investigation on the chemical constituents of the fruiting bodies of Ganoderma sinense were carried out and 63 compounds were isolated.On the basis of chemical evidences and spectral analyses([α],UV,CD,IR,1D-NMR,2D-NMR,MS),the structures of these compounds were elucidated as follows:ganosinensol E(1),ganosinensol A(2),ganosinensol B(3),ganosinensol F(4),ganosinensol G(5),ganosinensol H(6),ganosinensol I(7),ganosinensol C(8),ganosinensol D(9),ganosinensol J(10),ganosinensol K(11),ganosinensol L(12),ganosinensol M(13),(+)-ganosinlactone A(14),(-)-ganosinlactone A(15),(+)-ganosinlactone B(16),(-)-ganosinlactone B(17),(+)-ganosinlactone C(18),(-)-ganosinlactone C(19),tetraoxycitricolic acid(20),(22E,24R)-6β-methoxyergosta-7,9(11),22-triene-3β,5α-diol(21),(-)-lingzhiol(22),(+)-lingzhiol(23),(-)-lucidimine A(24),(+)-lucidimine A(25),lucidimine B(26),(-)-lucidimine C(27),(+)-lucidimine C(28),(-)-sinensine E(29),(+)-sinensine E(30),(-)-sinensine D(31),(+)-sinensine D(32),4(1H)-quinolinone(33),neoechinulin A(34),(4E,8E)-N-D-2’-hydroxy-palmitoyl-1-O-β-D-glycopyranosyl-9-methyl-4,8-sphingadienine(35),[1 S-[1R*(S*),2S*,3E,7E]]-N-[1-[(β-D-glucopyranosyloxy)methyl]-2-hydroxy-8-methyl-3,7-heptade cadienyl]-2-hydroxy-heptadecanamide(36),cerebroside D(37),(2R)-N-[(1S,2R,3E,7E)-1-[(β-D-glucopyranosyloxy)methyl]-2-hydroxy-8-methyl-3,7-heptadecadien-1-yl]-2-hydroxy-nonadecanamide(38),adenosine(39),uridine(40),hypoxanthine(41),2-hydroxy-5-carboxypyridine(42),(22E,24R)-ergosta-7,9(11),22-triene-3β,5α,6α-triol(43),ergosta-4,6,8(14),22-tetraen-3-one(44),ergosta-7,22-dien-3-one(45),(22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,22-dien-3β-ol(46),(22 E,24S)-5α,8αepidioxy-24-methyl-cholesta-6,9(11),22-trien-3β-ol(47),cyathisterol(8βhydroxyergosta-4,6,22-trien-3-one)(48),22E-7α-methoxy-5α,6α-epoxyergosta-8(14),22-dien-3β-ol(49),(22E,24R)-ergosta-7,9(11),22-triene-3β,5α,6β-triol(50),stigmasta-7,22-diene-3β,5α,6α-triol(51),(22E,24R)-ergosta-7,22-diene-3β,5α,6β-triol(52),22E-6β-methoxyergosta-7,22-diene-3β,5α-triol(53),3β-glucopyranosyl-5α,6βdihydroxyergosta-7,22-diene(54),methyl ganoderate A(55),methyl ganoderenic A(56),ganodermanontriol(57),1H-2-benzopyran-1-one,3,4-dihydro-6,7-dihydroxy(58),2-methy-6-hydroxychromogen(59),6-hydroxychromogen(60),(E)-p-coumaric acid(61),coenzyme Q9(62),1-methylcyclohexane-1,2,4-triol(63).Among them,21 compounds(1-21)were new compounds,and 8 compounds(33,34,42,58,59,60.62,63)were isolated for the first time from this genus.In this thesis,the systematic investigation on the chemical constituents of the fruiting bodies of Ganoderma lucidum were carried out and 55 compounds were isolated.On the basis of chemical evidences and spectral analyses([α],UV,CD,IR,1D-NMR,2D-NMR,MS),the structures of these compounds were elucidated as follows:12β-acetoxy-3β,31-dihydroxy-7,1 1,15,23-tetraoxo-5α-lanosta-8-en-26-oic acid(64),lucidenic acid R(65),methyl lucidenate K(66),methyl lucidenate L(67),7β,15α,20-trihydroxy-3,11,23-trioxo-5α-lanosta-8-en-26-oic acid(68),12acetoxyganoderic acid θ(69),methyl ganoderic E(70),methyl ganoderenic D(71),methyl ganoderenic F(72),ganoderic acid C(73),methyl ganolucidate C(74),ganoderic acid J(75),ganoderenic acid G(76),ganoderenic acid D(77),ganoderic acid I(78),ganoderic acid η(79),ganoderenic acid C(80),ganoderic acid ζ(81),ganoderenic acid A(82),methyl ganoderate C1(83),ganoderenic acid F(84),ganoderic acid E(85),ganoderic acid F(86),12β-acetoxy-3,7,11,15,23-pentaoxo-5a-lanosta-8,20-dien-26-oic acid methyl ester(87),ganoderenic acid K(88),12acetoxyganoderic acid D(89),7β-hydroxy-12β-acetoxy-3,11,15,23-tetraoxo-5αlanosta-8,20-dien-26-oic acid(90),12β-acetoxy-3,7,11,15,23-pentaoxo-5α-lanosta8,20-dien-26-oic acid(91),methyl ganoderate F(92),12β-acetoxy-7β-hydroxy-3,11,15,23-tetraoxo-5α-lanosta-8,20-dien-26-oic acid(93),methyl lucidenate D2(94),methyl lucidenate A(95),lucidenate acid F(96),butyl ganoderenic F(97),butyl ganoderenic A(98),butyl ganoderenic B(99),butyl ganoderic C6(100),butyl ganoderic I(101),butyl ganoderic H(102),butyl ganoderenic D(103),butyl lucidenate Q(104),butyl lucidenate A(105),butyl lucidenate D(106),butyl lucidenate E(107),ganoderiol F(108),ganodermenonol(109),ganomycin I(110),dibutyl malate(111),5-hydroxy-4-(4-hydroxyphenyl)-2(5H)-furanone(112),5hydroxy-4-phenyl-2(5H)-furanone(113),vanillic acid(114),gentisic acid(115),butyl p-hydroxybenzoic acid(116),butyl hematinic acid(117),cyclo-(Phe-Val)(118).Among them,6 compounds(64-69)were new compounds.Compounds isolated from Ganoderma sinense Zhao.Xu et Zhang and Ganoderma lucidum(Leyss.ex Fr.)Karst.were tested for inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages by Griess assay.Among the tested compounds,1-13 showed potent inhibitory activities against NO production.Compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines(BGC-823,A375 and Hep2)by MTT method.Compounds 2,3,10,11,14,15,27,28,75 and 95 were inactive against the three human cancer cell lines.This paper is important to reveal the chemical constituents of Ganoderma sinense Zhao.Xu et Zhang and Ganoderma lucidum(Leyss.ex Fr.)Karst.and their bioactivity,and will provide a basis for further development and utilization of this plant.