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.     

Tirucallane triterpenes from the roots of Ozoroa insignis

Eight tirucallane triterpenes, methyl 3alpha,24S-dihydroxytirucalla-8,25-dien-21-oate (2), methyl 3alpha-hydroxy-24-oxotirucalla-8,25-dien-21-oate (3), methyl 3alpha-hydroxy-25,26,27-trinor-24-oxotirucall-8-en-21-oate (4), 3alpha,25-dihydroxy-24-(2-hydroxyethyl)-tirucall-8-en-21-oic acid (5), 3alpha,24S,25-trihydroxytirucall-8-en-21-oic acid (6), 3alpha,24R,25-trihydroxytirucall-8-en-21-oic acid (7), 3alpha,25-dihydroxytirucall-8-en-21-oic acid (8), and methyl 3alpha,25-dihydroxytirucall-8-en-21-oate (9), together with alpha-elemolic acid methyl ester (1), were isolated from the roots of Ozoroa insignis. Their structures were elucidated on the basis of spectroscopic evidence.     

Triterpenoids from Sanguisorba officinalis

Seven triterpenoids, i.e., 3beta-[(alpha-L-arabinopyranosyl)oxy]-19beta-hydroxyurs-12,20(30)-dien-28-oic acid (1), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-11,13(18)-dien-28-oic acid beta-D-glucopyranosyl ester (2), 2alpha,3alpha,23-trihydroxyurs-12-en-24,28-dioic acid 28-beta-D-glucopyranosyl ester (3), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(20)-dien-28-oic acid (4), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(29)-dien-28-oic acid (5), 3beta-[(alpha-L-arabinopyranosyl)oxy]-19alpha-hydroxyolean-12-en-28-oic acid (6), 2alpha,3beta-dihydroxy-28-norurs-12,17,19(20),21-tetraen-23-oic cid (7), together with three known ones (8-10), were isolated from the roots of Sanguisorba officinalis. Their structures were determined by spectroscopic and chemical methods. Compounds 7 and 10 showed marginal inhibition activity against the growth of tumor cell lines.     

Litchi chinensis-derived terpenoid as anti-HIV-1 protease agent: structural design from molecular dynamics simulations

The molecular structures of the binding between human immunodeficiency virus-1 protease (HIV-1PR) and various inhibitors including existing extensive natural products extracts have been investigated for anti-HIV drug development. In this study, the binding of HIV-1PR and a terpenoid from Litchi chinensis extracts (3-oxotrirucalla-7,24-dien-21-oic acid) was investigated in order to clarify the inhibition effectiveness of this compound. Molecular dynamics (MD) simulations of HIV-1PR complex with 3-oxotrirucalla-7,24-dien-21-oic acid were performed including water molecules. The MD simulation results indicated the formation of hydrogen bonds between the oxygen atoms of the inhibitor and the catalytic aspartates, which are commonly found in inhibitors–protease complexes. On the other hand, no hydrogen bonding of this particular inhibitor to the flap region was found. In addition, the radial distribution function of water oxygens around the catalytic carboxylate nitrogens of Asp29 and Asp30 suggests that at least one or two water molecules are in the active site region whereas direct interaction of the inhibitor was found for catalytic carboxylate oxygen of Asp25. The results of this simulation, in comparison with the structures of other HIV-PR inhibitor complexes, could lead to a better understanding of the activity of 3-oxotrirucalla-7,24-dien-21-oic acid.     

The degradation of beta-sitosterol by Pseudomonas sp. NCIB 10590 under aerobic conditions

The bacterial degradation of beta-sitosterol by Pseudomonas sp NCIB 10590 has been studied. Major biotransformation products included 24-ethylcholest-4-en-3-one, androsta-1,4-diene-3,17-dione, 3-oxochol-4-en-3-one-24-oic acid and 3-oxopregn-4-en-3-one-20-carboxylic acid. Minor products identified were 26-hydroxy-24-ethylcholest-4-en-3-one, androst-4-ene-3,17-dione, 3-oxo-24-ethylcholest-4-en-26-oic acid, 3-oxochola-1,4-dien-3-one-24-oic acid, 3-oxopregna-1,4-dien-3-one-20 carboxylic acid and 9 alpha-hydroxyandrosta-1,4-diene-3,17-dione. Studies with selected inhibitors have enabled the elucidation of a comprehensive pathway of beta-sitosterol degradation by bacteria.     

A-seco-oleane-type triterpenes from Phomopsis sp. (strain HKI0458) isolated from the mangrove plant Hibiscus tiliaceus

From the fermentation broth of an unidentified Phomopsis sp. (strain HKI0458) isolated from the mangrove plant Hibiscus tiliaceus, four A-seco-oleane-type triterpenes, namely 3,4-seco-olean-11,13-dien-4,15alpha, 22beta,24-tetraol-3-oic acid (1), 3,4-seco-olean-11,13-dien-4,7beta,22beta,24-tetraol-3-oic acid (2), 3,4-seco- olean-13-en-4,7,15,22,24-pentaol-3-oic acid (3), and 3,4-seco-olean-13-en-4,15,22,24-tetraol-3-oic acid (4) were obtained. Their structures were elucidated by extensive spectroscopic (UV, IR, FABMS, and 2D NMR) data analyses.     

Constituents of the fungi Daedalea quercina and Daedaleopsis confragosa var. tricolor

Phytochemical examination of solvent extracts of the wood-rotting fungi Daedalea quercina and Daedaleopsis confragosa var. tricolor led to the isolation of five new triterpene derivatives and some known fungal constituents. All structures were identified by one- and two-dimensional NMR spectroscopy and mass spectrometry. From Daedalea quercina, the new natural products 16-O-acetylpolyporenic acid C, 16alpha-acetoxy-24-methylene-3-oxolanost-8-en-21-oic acid, (+)-24-methylene-3,23-dioxolanost-8-en-26-oic acid, (+)-3beta,12beta-dihydroxy-24-methyl-23-oxolanost-8-en-26-oi c acid and 12beta,23-epoxy-3alpha,23-dihydroxy-24-methyllanost-8- en-26-oic acid could be isolated. From Daedaleopsis confragosa var. tricolor, the compounds 3alpha-carboxyacetoxyquercinic acid, 3alpha-carboxyacetoxy-24-methylene-23-oxolanost-8-en-2 6-oic acid and 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol were identified. These are the first described triterpene derivatives isolated from this fungus.     

Tirucallane triterpenoids from Dysoxylum hainanense

Four tirucallane derivatives, 3beta,22S-dihydroxy-tirucalla-7,24-dien-23-one, 22,23-epoxy-tirucalla-7-ene-3beta,24,25-triol, 3beta,25-dihydroxy-tirucalla-7,23-diene, 23,26-dihydroxy-tirucalla-7,24-dien-3-one, together with two known triterpenoids, 24,25-epoxy-3beta,23-dihydroxy-7-tirucallene, tirucalla-7,24-diene-3beta,23-diol, were isolated from Dysoxylum hainanense. Their structures were elucidated on the basis of spectroscopic evidence.     

Dehydrotrametenonic acid and dehydroeburiconic acid from Poria cocos and their inhibitory effects on eukaryotic DNA polymerase alpha and beta

A new lanostane-type triterpene acid, (20xi)-3-oxolanosta-7,9(11),24-trien-21-oic acid (1; dehydrotrametenonic acid), along with a known triterpene acid, dehydroeburiconic acid (2), were isolated from the epidermis of the sclerotia of Poria cocos. The structure of 1 was analyzed on the basis of spectroscopic methods. Compounds 1 and 2 inhibited calf DNA polymerase alpha and rat DNA polymerase beta, with the 50% inhibition values of 45.5 microM (1) and 40.8 microM (2), and 86.5 microM (1) and 30.0 microM (2), respectively.     

飞龙掌血中三萜酸成分研究

从芸香科植物飞龙掌血中提取分离出4个新三萜酸,经波谱数据分析,分别鉴定为2α,3α,19α-trihydroxy11-oxo-urs-12-en-28-oic acid（1）,2α,3α,11α,19α-tetrahydroxy-urs-12-en-28-oic acid（2）,2α,3α-dillydroxy-19-oxo-18,19-seco-urs-11,13（18）-diene-28-oic acid（3）和2α,3α,19α-trihydroxy-olean-11,13（18）-dien-28-oic acid（4）。还分离鉴定出已知成分野鸭春酸（5）、arjunic acid（6）、飞龙掌血素、勒钩内脂和β-谷甾醇。     

Diterpenoids from the pericarp of Platycladus orientalis

Eight labdane-type diterpenes, 7beta,13S-dihydroxylabda-8(17),14-dien-19-oic acid (1), 12R,15-dihydroxylabda-8(17),13E-dien-19-oic acid (3c), 12R,15-dihydroxylabda-8(17),13Z-dien-19-oic acid (3d), 12R,13R,14S-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4a), 12S,13S,14R-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4b), 15-hydroxy-12-oxolabda-8(17),13E-dien-19-oic acid (5), 14R,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7a) and 14S,15-dihydroxylabda-8(17),12Z-dien-19-oic acid (7b), along with 20 known diterpenoids, were isolated from the pericarp of Platycladus orientalis. Their structures were unambiguously elucidated by NMR spectroscopic and single crystal X-ray diffraction analyses, as well as via chemical correlation conversion. NMR spectroscopic data of known isomers 8c and 8d were reported as a supplement to existing data.     

Studies on delta8-delta7 isomerization and methyl transfer of sterols in ergosterol biosynthesis of yeast.

The formation of cholesta-7,24-dien-3 beta-ol and its activity as a substrate for the sterol side-chain methyltransferase in yeast have not previously been studied. Experiments with acetone-powder extracts of yeast showed that the sterol is formed from zymosterol by delta8-delta7 isomerization. However, direct conversion of cholesta-7,24-dien-3 beta-ol into zymosterol could not be demonstrated. The reversibility of the reaction was proved by the detection of 3H-incorporation into cholesta-8-en-3 beta-ol (with lathosterol as a carrier) from [3H]H2O in the medium. Incubation of cholesta-7,24-dien-3 beta-ol and S-adenosyl-L-[methyl-14C]methionine with the acetone-powder extract resulted in methylation of the sterol to form episterol. Similar incubation of zymosterol gave fecosterol and episterol, suggesting that fecosterol initially formed by the methylation was isomerized to episterol. In intact cells, however, an alternative pathway (zymosterol yields cholesta-7,24-dien-3 beta-ol yields episterol) may also operate. The relative importance of the two pathways is not known.     

New A-nor steroids and their antifouling activity from the Chinese marine sponge Acanthella cavernosa

A chemical examination of the Chinese sponge Acanthella cavernosa resulted in the isolation of three new A-ring contracted steroids, the ethyl esters of 2beta-hydroxy-4,7-diketo-A-norcholest-5-en-2-oic acid (1), 24S-ethyl-2beta-hydroxy-4,7-diketo-A-norcholest-5-en-2-oic acid (2), and 2beta-hydroxy-4,7-diketo-24R-methyl-A-norcholest-5,22(E)-dien-2-oic acid (3), along with four other known steroids (4-7). The structures were determined on the basis of extensive spectroscopic analysis. Compounds 1-3 showed antifouling activity toward the settlement inhibition of Balanus albicostatus with the EC(50) values of 8.2, 23.5, 31.6 microg/mL, respectively.     

The biotransformation of ent-kaur-16-en-19-oic acid by Rhizopus stolonifer.

Microbial transformation of ent-kaur-16-en-19-oic acid was carried out with R. stolonifer. After seven days of incubation, two metabolites, ent-7 alpha-hydroxy-kaur-16-en-19-oic acid and ent-12 beta-hydroxy-kaur-9(11),16-dien-19-oic acid, were isolated as a result of hydroxylation and hydroxylation/dehydrogenation, respectively. Incubation for 15 days also afforded ent-16 beta,17-dihydroxy-kauran-19-oic acid. The metabolites were identified by spectroscopic methods.     

A novel olefinic rearrangement. The enzymic conversion of cholesta-7,9-dien-3β-ol into cholesta-8,14-dien-3β-ol

1. [3alpha-(3)H]Cholesta-7,9-dien-3beta-ol is converted in high yield into cholesterol by a 10000g(av.) supernatant fraction of rat liver homogenate. 2. Incubation of cholesta-7,9-dien-3beta-ol with [4-(3)H]NADPH and rat liver microsomal fractions under anaerobic conditions resulted in (3)H being incorporated into the 14alpha-position of cholest-7-en-3beta-ol. 3. Under anaerobic conditions in the absence of NADPH cholesta-7,9-dien-3beta-ol was isomerized into cholesta-8,14-dien-3beta-ol by rat liver microsomal fractions.     

Synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholanoic acids.

Chemical synthesis of 3 alpha,6 beta,7 alpha,12 beta- and 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholan-24-oic acids is described. 3 alpha,12 beta-Dihydroxy-5 beta-chol-6-en-24-oic acid used as the starting material in the synthesis was prepared via oxidation of 3 alpha,12 alpha-dihydroxy-5 beta-chol-6-en-24-oic acid 3-hemisuccinate at C-12 followed by reduction with potassium/tertiary amyl alcohol. alpha-Epoxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24-oic acid with m-chloroperbenzoic acid followed by cleavage of the epoxide with acetic acid and alkaline hydrolysis yielded 3 alpha,6 beta,7 alpha,12 beta-tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 25%). N-Methylmorpholine-N-oxide-catalyzed osmium tetroxide oxidation of the ester diacetate of 3 alpha,12 beta-dihydroxy-5 beta-chol-6-en-24-oic acid followed by alkaline hydrolysis yielded 3 alpha,6 beta,7 beta,12 beta-tetrahydroxy-5 beta-cholan-24-oic acid (overall yield 33%). The structures of the synthesized bile acids were confirmed from their proto nuclear magnetic resonance and mass spectral fragmentation patterns.     

Microbial thansformation of a mixture of argentatin A and incanilin

The biotransformation of a mixture of argentatin A (20%) 1 and incanilin (80%) 2 by Gibberella suabinetti ATCC 20193 and Septomyxa affinis ATCC 6737 demonstrated the conversion of incanilin to 16beta-hydroxylanosta-2, 8, 23-triene, while argentatin A did not react. The acetate of this triterpenoid mixture was biotransformed by Septomyxa affinis ATCC 6737 to give five metabolites. Argentatin A acetate was transformed to 3beta, 16beta,30-trihydroxycycloart-20, 24-diene, 20R, 24R-epoxy-16beta, 25-dihydroxy-3, 4-seco-cycloart-4(28)-en-3-oic acid acetate and 20R, 24R-epoxy-16beta, 25-dihydroxy-3, 4-seco-cycloart-4(28)-en-3-oic acid. Incanilin acetate was converted to 16beta-hydroxylanosta-2, 8, 23-triene and 20R, 24R-epoxy-16beta, 25-dihydroxy-3, 4-seco-lanost-1, 4(28), 8-trien-3-oic acid acetate. The structural elucidations of these metabolites were achieved by different spectroscopic methods.     

Sterols from Candida lipolytica yeast grown on n-alkanes

The sterols of Candida lipolytica grown on n-alkanes were isolated by reverse phase HPLC and found to be mainly ergosterol, with small quantities of ergost-7-en-3β-ol, ergosta-7,22-dien-3β-ol, ergosta-7,24(28)-dien-3β-ol and ergosta-5,7,9(11),22-tetraen-3β-ol.     

Sterols and triterpenes in cell culture of Hyssopus officinalis L

Cell suspension cultures from hypocotyl-derived callus of Hyssopus officinalis were found to produce two sterols i. e. beta-sitosterol (1) and stigmasterol (2), as well as several known pentacyclic triterpenes with an oleanene and ursene skeleton. The triterpenes were identified as oleanolic acid (3), ursolic acid (4), 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (5), 2alpha,3beta-dihydroxyurs-12-en-28-oic acid (6), 2alpha,3beta,24-trihydroxyolean-12-en-28-oic acid (7), and 2alpha,3beta,24-trihydroxyurs-12-en-28-oic acid (8). Compounds 5-8 were isolated as their acetates (6, 8) or bromolactone acetates (5, 7).