Friedolanostane, friedocycloartane and benzophenone constituents of the bark and leaves of Garcinia benthami

Friedolanostanes, (22Z,24E)-3β-acetoxy-9α-hydroxy-17,14-friedolanosta-14,22,24-trien-26-oic acid, (22Z,24E)-3β,9α-dihydroxy-17,14-friedolanosta-14,22,24-trien-26-oic acid, (22Z,24E)-9α-hydroxy-3-oxo-17,14-friedolanosta-14,22,24-trien-26-oic acid, a friedocycloartane, (22Z,24E)-3α-hydroxy-17,13-friedocycloarta-12,22,24-trien-26-oic acid, and a benzophenone, benthaphenone, together with known compounds (22Z,24E)-3α,9α-dihydroxy-17,13-friedolanosta-12,22,24-trien-26-oic acid, methyl (24E)-3α,23-dihydroxy-17,14-friedolanosta-8,14,24-trien-26-oate, glutinol, lupeol, and stigmasterol, were isolated from leaves and bark of Garcinia benthami. Their structures were elucidated using spectroscopic techniques, mainly 1-D and 2-D NMR spectroscopy, and chemical correlations.     

Cytotoxic and anti-angiogenic effects of lanostane triterpenoids from Ganoderma lucidum

Two new lanostane triterpenes, 3α,12β,15α-triacetoxy-5α-lanosta-7,9(11),24-trien-26-oic acid (1) and 5α-lanosta-8,24-diene-26,27-dihydroxy-3,7-dione (2), together with sixteen known compounds (3–18) were isolated from the fruiting bodies of the Vietnamese mushroom Ganoderma lucidum. Their chemical structures were determined by extensive spectroscopic (IR, HR-EI-MS, 1D and 2D NMR) analyses. Potential cytotoxic activities of these compounds were evaluated against human non-small cell lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), and prostatic small cell carcinoma (PC-3). Among the compounds, 3α,12β,15α-triacetoxy-5α-lanosta-7,9(11),24-trien-26-oic acid (1) showed significant cytotoxic activity against PC-3 cells with an IC₅₀ of 11.5 μM. In studies of anti-angiogenesis activity, ganoderic acid F (17) was found to have the most potent inhibitory effect on the formation of capillary-like structures of human umbilical vein endothelial cells.     

一种无孢灵芝菌丝体的活性成分

利用制备型高效液相、凝胶层析、制备型薄层色谱等方法对无孢灵芝龙芝2号的固体发酵菌丝体进行分离纯化,通过波谱分析,化合物分别鉴定为灵芝酸P（1）,灵芝酸T1（2）,灵芝酸Mk（3）,灵芝酸S（4）,灵芝酸T（5）,ganodermanondiol（6）,灵芝酸Me（7）,5α, 8α-epidioxyergosta-6, 22-dien-3β-ol（8）,灵芝酸R（9）,lanosta-7, 9(11), 24-trien-3α-hydroxy-26-oic acid（10）,ganodermenonol（11）。其中灵芝酸T1为首次发现的天然产物。体外细胞实验证实,11种化合物对肿瘤细胞L1210的增殖均有很强的抑制作用,其增殖抑制的IC₅₀值均在39.69μmol/L以下。     

石菖蒲的化学成分研究

运用色谱法从石菖蒲根茎提取物中分离得到18个化合物,经波谱学分析鉴定为:(7S,8R)-4,9’-di-hydroxyl-3,3’-dimethoxyl-7,8-dihydrobenzofuran-1’-propylneolignan(1),(7S,8R)-4,9’-dihydroxyl-3,3’-dimethoxyl-7,8-dihydrobenzofuran-1’-propylneoligan-9-O-β-D-glucopyranoside(2),7’-hydroxylariciresinol-9-acetate(3),5-羟基-3,7,4’-三甲氧基黄酮(4),野漆树苷(5),紫云英苷(6),松属素-3-O-芸香糖苷(7),山奈酚-3-O-芸香糖苷(8),德钦红景天苷(9),isoschaftoside(10),5-羟甲基糠醛(11),反式桂皮酸(12),3,7-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oicacid(13),3,7-dihydroxy-11,15,23-trioxo-lanost-8,16-dien-26-oic acid methyl ester(14),环阿屯醇(15),胡萝卜苷(16),羽扇豆醇(17),(22E,24R)-ergosta-5,7,22-trien-3β-ol(18)。除化合物4、11和16外,其余15个化合物均为首次从该植物中分离得到。     

Synthesis of homoursodeoxycholic acid and [11,12-3H]homoursodeoxycholic acid

Homoursodeoxycholic acid and [11,12-³H]homoursodeoxycholic acid were synthesized from ursodeoxycholic acid and homocholic acid, respectively. Ursodeoxycholic acid (Ia) was converted to 3α,7β-diformoxy-5β-cholan-24-oic acid (Ib) using formic acid. Reaction of the diformoxy derivative (Ib) with thionyl chloride yielded the acid chloride (II) which was treated with diazomethane to produce 3α,7β-diformoxy-25-diazo-25-homo-5β-cholan-24-one (III). Homoursodeoxycholic acid (IV) was formed from the diazoketone (III) by means of the Wolff rearrangement of the Arndt-Eistert synthesis.N-Bromosuccinimide oxidation of homocholic acid (V), which was prepared from cholic acid by the same procedure described above, afforded 3α,12α-dihydroxy-7-oxo-25-homo-5β-cholan-25-oic acid (VI). Reduction of the 7-ketohomodeoxycholic acid (VI) with sodium in 1-propanol gave 3α,7β,12α-trihydroxy-25-homo-5β-cholan-25-oic acid (VII). The methyl ester of 7-epihomocholic acid (VII) was partially acetylated to give methyl 3α,7β-diacetoxy-12α-hydroxy-25-homo-5β-cholan-25-oate (VIII) using a mixture of acetic anhydride, pyridine and benzene. Dehydration of the diacetoxy derivative (VIII) with phosphorus oxychloride yielded methyl 3α,7β-diacetoxy-25-homo-5β-chol-11-en-25-oate (IX). Reduction of the unsaturated ester (IX) with tritium gas in the presence of platinum oxide catalyst followed by alkaline hydrolysis gave [11,12-³H]homoursodeoxycholic acid.     

Constituents of various wood-rotting basidiomycetes

Phytochemical investigation of n-hexane and methanol extracts of fruiting bodies of the wood-rotting fungi Fomitopsis pinicola. Ganoderma lipsiense, Fomes fomentarius and Gloeophyllum odoratum led to the isolation and identification of several triterpene derivatives and some aromatic compounds derived from lignin. These are the new natural products, namely, pinicolic acid E (16alpha-hydroxy-3-oxolanosta-8,24-dien-21-oic acid) and pinicolol C (3-oxolanosta-7,9(11),24-trien-15alpha,21-diol) from the crust of F. pinicola, ganoderenic acid D [(E)-7beta-hydroxy-3,11,15,23-tetraoxolanosta-8,20(22)-di en-26-oic acid] and ganoderic acid N (7beta,20-dihydroxy-3,11,15,23-tetraoxolanost-8-en-26-oic acid) from G. lipsiense and ergosterol peroxide (5alpha,8alpha-epi-dioxyergost-6-en-3beta-ol) as well as ergost-7-en-3-one from F. fomentarius. From G. odoratum, dehydroeburicoic acid [24-methylene-3-oxolanosta-7,9(11)-dien-21-oic acid], the dimethylacetal of 4,4,14alpha-trimethyl-24-oxo-5alpha-chol-8-en-21-oic acid and some aromatic compounds, of which 1-(4'-methoxyphenyl)-1,2-ethandiol is a new natural product, were isolated. Furthermore, a complete set of 13C NMR data of the steryl esters 3beta-linoleyloxyergosta-7,24(28)-diene, 3beta-linoleyloxyergosta-7,24-diene and 3beta-linoleyloxyergost-7-ene, which could be identified as a mixture in all investigated fungi, could be recorded. It was proved by HPLC and TLC investigations, that the crust on top of the fruiting bodies of F. pinicola consists of lanostane derivatives.     

New Bitter C27 and C30 Terpenoids from the Fungus Ganoderma lucidum (Reishi)

Four new bitter terpenoids, lucidenic acids A (1), B (2), C (3) and ganoderic acid C (5), were isolated from the fruiting bodies of Ganoderma lucidum, together with the known bitter ganoderic acid B (4). On the basis of spectroscopic data and chemical conversion, their structures were determined to be 7β-hydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oic acid, 7β,12β-dihydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oic acid, 3β,7β,12β-trihydroxy-4,4,14α-trimethyl-11,15-dioxo-5α-chol-8-en-24-oic acid and 7β-hydroxy-3,11,15,23-tetraoxo-5α-lanost- 8-en-26-oic acid, respectively.     

The isolation of lanosta-7,9(11),24-trien-3β,21-diol from the fungus ganoderma australe

The lipid-soluble fraction of the fungus Ganoderma australe belonging to the family Polyporaceae has yielded ergosterol palmitate, ergosta-7,22-dien-3-one, ergosterol and lanosta-7,9(11),24-trien-3β,21-diol. This fungus is the second reported natural source of the latter compound whose structure is now established on the basis of spectral data.     

Stereochemistry of strictic acid and related furano-diterpenes from conyza japonica and grangea maderaspatana

Extraction of Conyza japonica gave strictic acid, ent-2β-hydroxy-15,16-epoxy-3,13(16),14-clerodatrien-18-oic acid and 5,7-dihydroxy-3,8,4′-trimethoxyflavone. Extraction of Grangea maderaspatana gave (-)-hardwickiic acid, ent-15,16-epoxy-1,3,13(16),14-clerodatetraen-18-oic acid and 3-hydroxy-8-acetoxypentadeca-1,9,14-trien-4,6-diyne. The structure of ent-2β-hydroxy-15,16-epoxy-3,13(16),14-cleroclatrien-18-oic acid was deduced by spectroscopic methods and by partial synthesis from (-)-hardwickiic acid and the stereochemistries of strictic acid and (ent-15,16-epoxy-1,3,13(16),14-clerodatraen-18-oic acid were established by correlation with ent-2β-hydroxy-15,16-epoxy-3,13(16),14-clerodatrien-18-oic acid.     

Metabolism of (24R and 24S)-27-nor-24-methyl-3α,7α-dihydroxy-5β-cholestan-26-oic acids and 27-nor-3α,7α-dihydroxy-5β-cholestan-26-oic acid in guinea pigs

[7β-³H]-(24R and 24S)-27-nor-24-methyl-3α,7α-dihydroxy-5β-cholestan-26-oic acids and [7β-³H]-27-nor-3α,7α-dihydroxy-5β-cholestan-26-oic acid (C₂₇ and C₂₆ bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3α,7α-dihydroxy-5β-cholestan-26-oic-acid) were synthesized and administered intraperitoneally to bile fistula guinea pigs. The biliary bile acids formed were hydrolyzed and analyzed by thin layer chromatography, and the metabolites were identified by the inverse isotope dilution method. The results showed that both (24R and 24S)-27-nor-24-methyl-3α,7α-dihydroxy-5β-cholestan-26-oic acids were not metabolized by the liver and were excreted unchanged as their taurine and glycine conjugates whereas 27-nor-3α,7α-dihydroxy-5β-cholestan-26-oic acid was converted to chenodeoxycholic acid.     

灵芝菌丝体中一个三萜类化合物的核磁归属及活性初探

通过液体振荡-静置两阶段发酵获得灵芝菌丝体,并采用硅胶柱色谱层析、反相柱层析和甲醇重结晶的方法,从中分离得到4个三萜类化合物。根据NMR、MS等波谱数据分析,化合物分别被鉴定为lanosta-7,9(11),24-trien-3α-acetoxy-26-oic acid（1）、灵芝酸R（2）、灵芝酸T（3）和灵芝酸S（4）,其中化合物1的核磁信号全归属为首次报道。4个三萜类化合物均具有较好的抑制肿瘤细胞L1210及K562增殖的活性,且化合物1的体外抗肿瘤活性为首次证实,其对肿瘤细胞L1210及K562增殖的半数抑制浓度IC₅₀分别为22.17μmol/L和54.79μmol/L。     

Trichothecene mycotoxins from Fusarium sulphureum

Four mycotoxins isolated from moulded maize cultures of Fusarium sulphureum have been characterized as 3α,4β,15-triacetoxy-12,13-epoxytrichothec-9-ene, 4β,15-diacetoxy-3α-hydroxy-12,13-epoxytrichothec-9-ene, 15-acetoxy-3α,4β-dihydroxy-12,13-epoxytrichothec-9-ene and 4β-acetoxy-3α,15-dihydroxy-12,13-epoxytrichothec-9-ene.     

Biotransformation of 7α-hydroxy- and 7-oxo-ent-atis-16-ene derivatives by the fungus Gibberella fujikuroi

The microbiological transformation of 7α,19-dihydroxy-ent-atis-16-ene by the fungus Gibberella fujikuroi gave 19-hydroxy-7-oxo-ent-atis-16-ene, 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene, 7α,11β,19-trihydroxy-ent-atis-16-ene and 7α,16β,19-trihydroxy-ent-atis-16-ene, while the incubation of 19-hydroxy-7-oxo-ent-atis-16-ene afforded 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene and 16β,17-dihydroxy-7-oxo-ent-atisan-19-al. The biotransformation of 7-oxo-ent-atis-16-en-19-oic acid gave 6β-hydroxy-7-oxo-ent-atis-16-en-19-oic acid, 6β,16β,17-trihydroxy-7-oxo-19-nor-ent-atis-4(18)-ene and 3β,7α-dihydroxy-6-oxo-ent-atis-16-en-19-oic acid.     

Glechomanolides and eudesmanolides from Smyrnium perfoliatum

In addition to five known sesquiterpenoids, six new compounds were isolated from Smyrnium perfoliatum. The new compounds were 1β-acetoxy-eudesma-3,7(11),8-trien-8,12-olide, 1β-acetoxyeudesma-4(15),7(11),8-trien-8,12-olide, 1β-10α;4α,5β-diepoxy-8β-isobutoxy-glechomanolide, 1β, 10α;4α,5β-diepoxy-8α-isobutoxy-glechomanolide, 1β,4α-dihydroxy-2α,3α-epoxy-eudesma-7(11),8-dien-8,12-olide, 1β,4α-dihydroxy-2α,3α-epoxy-8β-methoxy-eudesma-7(11)-en-8α,12-olide.     

Ganoderiol A and B,New Triterpenoids from the Fungus Ganoderma lucidum (Reishi)

Two new lanostane-type triterpenoids, ganoderiol A (1) and ganoderiol B (2) were isolated from the fruiting bodies of Ganoderma lucidum, together with known ganodermanontriol (3) and ganodermatriol (4). The compounds were identified as 5α-lanosta-7,9(11)-dien-3β,24,25,26-tetraol (1), 15α,26,27-trihydroxy-5α-lanosta-7,9(11),24-trien-3-one (2), 24,25,26-trihydroxy-5α-lanosta-7,9(11)-dien-3-one (3) and 5α-lanosta-7,9(ll),24-trien-3β,26,27-triol (4), respectively.     

Microbial transformation of acetyl-11-keto-β-boswellic acid and their inhibitory activity on LPS-induced NO production

The capabilities of 20 strains of fungi to transform acetyl-11-keto-β-boswellic (AKBA) were screened. And biotransformation of AKBA by Cunninghamella blakesleana AS 3.970 afforded five metabolites (1–5), while two metabolites (6, 7) were isolated from biotransformation of Cunninghamella elegans AS 3.1207. The chemical structures of these metabolites were identified by spectral methods including 2D NMR and their structures were elucidated as 7β-hydroxy-3-acety-11-keto-β-boswellic acid (1), 21β-dihydroxy-3-acety-11-keto-β-boswellic acid (2), 7β,22α-dihydroxy-3-acety-11-keto-β-boswellic acid (3), 7β,16α-dihydroxy-3-acety-11-keto-β-boswellic acid (4), 7β,15α-dihydroxy-3-acety-11-keto-β-boswellic acid (5); 7β,15α,21β-trihydroxy-3-acety-11-keto-β-boswellic acid (6) and 15α,21β-dihydroxy-3-acety-11-keto-β-boswellic acid (7). All these products are previously unknown. Their primary structure–activity relationships (SAR) of inhibition activity on LPS-induced NO production in RAW 264.7 macrophage cells were evaluated.     

Antiplasmodial and other constituents from four Indonesian Garcinia spp.

Phytochemical investigations of four Garcinia spp. from Indonesia, i.e. Garcinia griffithii T. Anderson, Garcinia celebica L., Garcinia cornea L. and Garcinia cymosa K. Schum (Clusiaceae), have resulted in the isolation of a xanthone, 1,5-dihydroxy-3,6-dimethoxy-2,7-diprenylxanthone, 1,7-dihydroxyxanthone, isoxanthochymol, β-sitosterol-3-O-β-d-glucoside and stigmasterol-3-O-β-d-glucoside from the stem bark of G. griffithii; friedelin and 3β-hydroxy-23-oxo-9,16-lanostadien-26-oic acid or garcihombronane D from leaves of G. celebica; 23-hydroxy-3-oxo-cycloart-24-en-26-oic acid and epicatechin from stem bark of G. cornea; (±)-morelloflavone, morelloflavone-7-O-β-d-glucoside or fukugiside, the triterpene 3β-hydroxy-5-glutinen-28-oic acid and canophyllol from stem bark of G. cymosa. The xanthone and garcihombronane D displayed a selective activity against Plasmodium falciparum; isoxanthochymol and the triterpene β-hydroxy-5-glutinen-28-oic acid a broad but non-selective antiprotozoal activity.     

Synthesis of (4-C)-labeled and non-labeled 3β,15α-dihydroxy-5-pregnen-20-one and 3β,15α-dihydroxy-5-androsten-17-one

The synthesis of labeled and non-labeled 3β,15α-dihydroxy-5-pregnen-20-one (V) and 3β, 15α-dihydroxy-5-androsten-17-one (XI) is described. Treatment of 15α-hydroxy-4-pregnene-3,20-dione (I) with acetic anhydride and acetyl chloride gave 3,15α-diacetoxy-3,5-pregnadien-20-one (II). The enol acetate (II) was ketalized by a modification of the general procedure to yield 3,15α-diacetoxy-3,5-pregnadien-20-one cyclic ethylene ketal (III) which was then reduced with NaBH₄ and LiAlH₄ to give 3β, 15α-dihydroxy-5-pregnen-20-one cyclic ethylene ketal (IV). Cleavage of the ketal group of IV gave V. Similarly, XI was prepared by starting with 15α-hydroxy-4-androstene-3,17-dione (VII). The (4-¹⁴C)-3β,15α-dihydroxy-5-pregnen-20-one was prepared by a modification of the above procedure in that the enol acetate (II)was directly reduced with NaBH₄ and LiAlH₄ to yield 5-pregnene-3β,15α,20β-triol (XIII) which was then oxidized enzymatically with 20β-hydroxysteroid dehydrogenase to V.     

Integrifolin,a guaianolide from Andryala integrifolia

Integrifolin, the major constituent of Andryala integrifolia, has been isolated and characterized as 3β,8β-dihydroxy-4(15),10(14),11(13)-trien-(1αH), (5αH) guaian-6,12-olide (8-epi-desacylcynaropicrin).