Three new pentacyclic triterpenes and some flavonoids from the fruits of an Indian Ayurvedic plant Dendrophthoe falcata and their estrogen receptor binding activity

Extensive chromatographic screening of extracts of the fruits of the Indian Ayurvedic plant, Dendrophthoe falcata, resulted in the isolation of three new triterpenes, 3beta-acetoxy-1beta-(2-hydroxy-2-propoxy)-11alpha-hydroxy-olean-12-ene (1), 3beta-acetoxy-11alpha-ethoxy-1beta-hydroxy-olean-12-ene (2) and 3beta-acetoxy-1beta-hydroxy-11alpha-methoxy-olean-12-ene (3) along with nine known compounds, 3beta-acetoxy-1beta,11alpha-dihydroxy-olean-12-ene (4), 3beta-acetoxy-1beta,11alpha-dihydroxy-urs-12-ene (5), 3beta-acetoxy-urs-12-ene-11-one (6), 3beta-acetoxy-lup-20(29)-ene (7), 30-nor-lup-3beta-acetoxy-20-one (8), (20S)-3beta-acetoxy-lupan-29-oic acid (9), kaempferol-3-O-alpha-L-rhamnopyranoside (10), quercetin-3-O-alpha-L-rhamnopyranoside (11), and gallic acid (12). The structures of these compounds were determined using 1D and 2D NMR and high resolution electrospray mass spectrometry. These compounds were assayed for binding to estrogen receptors-alpha and beta and kaempferol-3-O-alpha-L-rhamnopyranoside (10) was found to be a ligand for both receptors with greater affinity for beta. The triterpenes (1-9) are reported for the first time in the genus Dendrophthoe and assumes taxonomic significance.     

Six new ursane- and oleanane-type triterpenes from the aerial roots of Ficus microcarpa

Four new ursane-type triterpenes, 3beta-acetoxy-11alpha-methoxy-12-ursene (1), 3beta-acetoxy-11alpha-ethoxy-12-ursene (2), 3beta-acetoxy-11alpha-hydroperoxy-12-ursene (3), 3beta-hydroxy-11alpha-hydroperoxy-12-ursene (4), and two new oleanane-type triterpenes, 3beta-acetoxy-11alpha-ethoxy-12-oleanene (5), 3beta-acetoxy-111alpha-hydroperoxy-12-oleanene (6), together with 3beta-acetoxy-11alpha-hydroxy-12-ursene (7), 3beta,11alpha-diacetoxy-12-ursene (8), 3beta-acetoxy-11alpha-hydroxy-12-oleanene (9), were isolated from the aerial roots of Ficus microcarpa L. f. Their structures were elucidated by spectroscopic and chemical methods.     

New cyclopropyl-triterpenoids from the aerial roots of Ficus microcarpa

Four new cyclopropyl-triterpenes, 27-nor-3beta-hydroxy-25-oxocycloartane (1), (22E)-25,26,27-trinor-3beta-hydroxycycloart-22-en-24-al (2), 3beta-acetoxy-15alpha-hydroxy-13,27-cyclours-11-ene (3), 3beta-acetoxy-12alpha-formyloxy-13,27-cycloursan-11alpha-ol (4), together with (23E)-27-nor-3beta-hydroxycycloart-23-en-25-one (5) were isolated from the aerial roots of Ficus microcarpa. Compounds 3 and 4 are rare 13,27-cycloursane-type triterpenes. Their structures were elucidated by spectroscopic and chemical methods.     

The microbial hydroxylation of levonorgestrel

The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta, 17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha-17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl-11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata afforded compound 2 as a major metabolise. These metabolites were structurally characterized on the basis of spectroScopic techniques. Metabolite 6 was identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2 and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values ranging between 9.4 and 309.8 microM.     

Saponins with an Unusual Secoursene Skeleton from Sesamum alatum THONN.

Three new saponins, alatoside A–C ( 4a, 5 , and 6a , resp.), with a 18,19-secours-12-ene skeleton were isolated from the aerial parts of Sesamum alatum THONN . (Pedaliaceae) by preparative liquid chromatography. Their structures were elucidated by spectroscopic methods, including X-ray diffraction analysis, and by chemical degradation (acidic and enzymatic hydrolyses). In addition, verbascoside ( 1 ) and two cyclohexylethanol derivatives, rengyol ( 2a ) and isorengyol ( 3a ), were isolated and identified.     

Dammarane triterpenes of Commiphora confusa resin

Fractionation of a steam distilled residue of Commiphora confusa resin has yielded four novel dammarane triterpenes characterised as (20S)-3beta-acetoxy-12beta,16beta-trihydroxydammar-24-ene, (20S)-12beta,16beta-trihydroxydammar-24-ene-3beta-O-beta-glucopyranoside, (20S)-3beta-acetoxy-12beta,16beta,25-tetrahydroxydammar-23-ene, and (20S)-3beta,12beta,16beta,25-pentahydroxydammar-23-ene. The known compounds beta-amyrin, 3beta-amyrinacetate, 2-methoxyfuranodienone, 2-acetoxyfuranodienone, (20R)-3beta-acetoxy-16beta-dihydroxydammar-24-ene, (20R)-3beta,16beta-trihydroxydammar-24-ene, 3beta-acetoxy-16beta-hydroxydammar-24-ene, 3beta-hydroxydammar-24-ene, 3beta-acetoxydammar-24-ene, and beta-sistosterol were also isolated from the same extract. The structures of the compounds were determined using spectroscopic, physical, and chemical methods.     

Total synthesis of (+/-)-stenine using the IMDAF cycloaddition of a 2-methylthio-5-amido-substituted furan

[reaction: see text]. The intramolecular [4 + 2]-cycloaddition of a 2-methylthio-5-amidofuran was used to create the azepinoindole skeleton present in the Stemona alkaloid stenine. The rearranged cycloadduct was converted to stenine (1) in 11 additional steps via a sequence that features a Crabtree catalyst directed hydrogenation (9-->10), iodolactonization (2-->11), and a Keck allylation (11-->12).     

Further bisabolenes and dammarane triterpenes of Commiphora kua resin

From the resins of Commiphora kua a novel bisabolene; 6-hydroxy-2-methyl-5-(5'-hydroxy-1'(R),5'-dimethylhex-3'-enyl)-phenol together with two new dammarane triterpenes, 3beta,16beta,20(S),25-tetrahydroxydammar-23-ene and 3beta-acetoxy-16beta,20(S),25-trihydroxydammar-23-ene, have been isolated. In addition, being reported are known compounds identified as 2-methyl-5-(4'(S)-hydroxy-1'(R),5'-dimethylhex-5'-enyl)-phenol, 2-acetoxyfuranodienone, 2-methoxyfuranodienone, 3beta,16beta,20(R)-trihydroxydammar-24-ene and its acetate derivative, 3beta-acetoxy-16beta,20(R)-dihydroxydammar-24-ene, and beta-amyrin and its acetate derivative. 2-Methyl-5-(4'(S)-hydroxy-1'(R),5'-dimethylhex-5'-enyl)-phenol displayed fungicidal activity against Cladosporium cucumernum on TLC assay.     

Anti-androgenic triterpenoids from the Brazilian medicinal plant, Cordia multispicata

Compounds 1-6 were isolated from the AcOEt soluble fraction of leaves of the Brazilian medicinal plant, Cordia multispicata, and their structures were elucidated to be 3beta,25-epoxy-21beta-acetoxy-3alpha,22beta-dihydroxyurs-12-en-28-al (1), 3beta,25-epoxy-28-acetoxy-3alpha,21beta,22beta-trihydroxyurs-12-ene (2), 21beta-acetoxy-22beta-hydroxy-3-oxours-12-en-28-al (3), 28-acetoxy-6beta, 21beta,22beta-trihydroxy-3-oxours-12-ene (4), 21beta,22beta-dihydroxy-3-oxours-1 2-en-28-al (5) and 3beta,21beta,22beta-trihydroxyurs-I2-en-28-al (6), respectively, by means of spectral data, especially two dimensional NMR techniques. Triterpenes having the hemiketal structure at the A-ring, an acyloxy group at C-22 and/or ketone at C-3 showed potent anti-androgenic activity.     

19-nor-11-Oxooleanan-12-ene and 18,19-seco-19-oxours-11,13(18)-diene triterpenes from Diospyros decandra bark

Four new triterpenes, 2α,3β-dihydroxy-19-nor-11-oxo-20-dimethylurs-12-en-24,28-dioic acid (equivalent to 2α,3β-dihydroxy-19-nor-11-oxoolean-12-en-24,28-dioic acid), 2α,3β-dihydroxy-18,19-seco-19-oxours-11,13(18)-dien-24,28-dioic acid, 2α,3β,19α-trihydroxy-11-oxours-12-en-24,28-dioic acid and 2α,3β,19α-trihydroxy-28-1′-β-d-[glucopyranosyl-(1″→6′)-glucopyranosyl]-urs-12-en-24,28-dioic acid were isolated from the methanol extract of the bark of Diospyros decandra as their acetate-methyl ester derivatives. The first two compounds represent the biosynthetic transformation products of 2α,3β,19-trihydroxyurs-24,28-dioic acid via oxidative rearrangement of ring E.     

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.     

Highly efficient total synthesis of the marine natural products (+)-avarone, (+)-avarol, (-)-neoavarone, (-)-neoavarol and (+)-aureol

Biologically important and structurally unique marine natural products avarone (1), avarol (2), neoavarone (3), neoavarol (4) and aureol (5), were efficiently synthesized in a unified manner starting from (+)-5-methyl-Wieland-Miescher ketone 10. The synthesis involved the following crucial steps: i) Sequential BF(3)Et(2)O-induced rearrangement/cyclization reaction of 2 and 4 to produce 5 with complete stereoselectivity in high yield (2 --> 5 and 4 --> 5); ii) strategic salcomine oxidation of the phenolic compounds 6 and 8 to derive the corresponding quinones 1 and 3 (6 --> 1 and 8 --> 3); and iii) Birch reductive alkylation of 10 with bromide 11 to construct the requisite carbon framework 12 (10 + 11 --> 12). An in vitro cytotoxicity assay of compounds 1-5 against human histiocytic lymphoma cells U937 determined the order of cytotoxic potency (3 > 1 > 5 > 2 > 4) and some novel aspects of structure-activity relationships.     

Canataxpropellane, a novel taxane with a unique polycyclic carbon skeleton (tricyclotaxane) from the needles of Taxus canadensis

A novel taxane with an unprecedented 5/5/4/6/6/6-membered hexacyclic skeleton containing [3.3.2]propellane was isolated from the needles of the Canadian yew, Taxus canadensis. The structure was established as 2α,10β-diacetoxy-5α,9α,20α-trihydroxy-3α,11α;4α,12α;14α,20-tricyclotaxan-13-one (1), which exists as two conformational isomers on the basis of spectroscopic analysis. This compound would be biogenetically derived from a normal 6/8/6-taxane by the intramolecular aldol reaction and [2+2] cycloaddition.     

Models for Taxol Biosynthesis: SeO2 Oxidation of Taxadiene

Together with the expected mono‐oxidized taxa‐4(20),11(12)‐diene‐5‐ol (1) and taxa‐4(5),11,20‐diene‐20‐ol (2), a new taxane skeleton, 3,12‐cyclotaxane (3), was obtained from chemical oxidation of taxadiene by selenium dioxide/t‐butylhydroperoxide.     

Aculeoside I, a novel 18,19-seco-ursane saponin isolated from Ilex aculeolata

A novel 18,19-seco-ursane saponin, aculeoside I (1), in addition to four known saponins were isolated from the leaves of Ilex aculeolata Nakai and identified by using spectroscopic and chemical methods. The structure of the new saponin was established as 3,19-dihydroxyl-16,21-epoxy-18,19-seco-13(18)-urs-ene-28-oic-acid-19-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranoside.     

Pregnane glycosides and steroid saponins from Smilax bockii Warb. and their NGF-potentiating activity

The chemical constituents of the roots of Smilax bockii Warb. were investigated and two pregnane glycosides and three steroid saponins were isolated. Their structures were established as 3beta-hydroxypregna-5,16-dien-20-one-3-O-alpha-L-rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (1), 3beta-hydroxypregna-5,16-dien-20-one-3-O-alpha-L-rhamnopyranosyl(1 --> 2)-[alpha-L-rhamnopyranosyl(1 --> 4)]-beta-D-glucopyranoside (2), dioscin (3), methyl protodioscin (4), 26-O-beta-D-glucopyranosyl-22alpha-methoxyl-(25R)-furost-5-en-3beta, 26-diol 3-O-alpha-L-rhamnopyranosyl(1 --> 4)-alpha-L-rhamnopyranosyl(1 --> 4)-[alpha-L-rhamnopyranosyl(1 --> 2)]-beta-D-glucopyranoside (5) on the basis of spectral analysis and chemical methods. Compound 1 is a new natural product and compounds 2, 5 were first isolated from the genus Smilax. Compound 5 showed enhancing activity of nerve growth factor (NGF)-induced neurite outgrowth in PC 12D cells.     

Structural determination of a new 2(3 --> 20)abeotaxane with an unusual 13beta-substitution pattern and a new 6/8/6-ring taxane from Taxus cuspidata

A new 2(3 --> 20)abeotaxane with an unusual 13beta-substitution pattern and a new 6/8/6-ring taxane were isolated from the methanol extract of the needles of Taxus cuspidata. The structures were established as 2alpha,7beta-diacetoxy-5alpha,10beta,13beta-trihydroxy-2(3 --> 20)abeotaxa-4(20), 11-dien-9-one (1) and 2alpha,5alpha,7beta,9alpha,13alpha-pentahydroxy-10beta-acetoxytaxa-4(20),11-diene (2) on the basis of 1D and 2D NMR spectral data and high-resolution FAB-MS analyses.     

Cytotoxic diterpenoids from Vietnamese medicinal plant Croton tonkinensis GAGNEP

Six new ent-kaurane-type diterpenoids were isolated from the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae) together with three known ent-11alpha-acetoxy-7beta,14alpha-dihydroxykaur-16-en-15-one (1), ent-kaur-16-en-15-one 18-oic acid (5) and ent-18-hydroxykaur-16-ene (7). Their structures were determined by spectroscopic analyses to be ent-7beta-acetoxy-11alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-11alpha-hydroxykaur-16-en-15-one (3), ent-11alpha-acetoxykaur-16-en-18-oic acid (4), ent-15alpha,18-dihydroxykaur-16-ene (6), ent-11alpha,18-diacetoxy-7beta-hydroxykaur-16-en-15-one (8), and ent-(16S)-1alpha,14alpha-diacetoxy-7beta-hydroxy-17-methoxykauran-15-one (14). ent-Kaurane-type diterpenoids from Croton tonkinensis 2-4, 6, and 9-13, were tested for toxicity in the brine shrimp lethality assay. Compounds 9, 10, and 12 demonstrated significant activity, compounds 2, 3, 6, and 11 showed weak activity, and compounds 4 and 13 were inactive.     

Fargosides A-E, triterpenoid saponins from Holboellia fargesii

Five new triterpenoid saponins, fargosides A, B, C, D, and E, were isolated from the roots of Holboellia fargesii. The structures of fargosides A-E were elucidated on the basis of chemical and physicochemical evidence and found to be 3beta,20alpha-dihydroxy-29-norolean-12-en-28-oic acid 3-O-beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranoside (1), 3beta,20alpha,24-trihydroxy-29-norolean-12-en-28-oic acid 23-O-beta-D-fucopyranosyl-(1-->2)-[alpha-L-arabinopyranosyl-(1-->3)]-beta-D-glucopyranoside (2), 3beta,23-dihydroxy-30-norolean-2,20(29)-dien-28-oic acid 3-O-alpha-L-arabinopyranosyl-(1-->2)-[beta-D-glucopyranosyluronic acid-(1-->3)]-alpha-L-arabinopyranoside (3), 3beta,23-dihydroxy-30-norolean-12,20(29)-dien-28-oic acid 3-O-methyl beta-D-glucopyranosyluronate-(1-->3)-alpha-L-arabinopyranoside (4), and 3beta,23-dihydroxy-olean-12-en-28-oic acid 3-O-methyl beta-D-glucopyranosyluronate-(1-->3)-alpha-L-arabinopyranoside (5), respectively.     

Three new taxoids from the leaves of the Japanese yew, Taxus cuspidata

Three new taxane diterpenoids were isolated from the leaves of the Japanese yew, Taxus cuspidta. Their structures were established as 5 alpha,13 alpha-diacetoxy-taxa-4(20),11-diene-9 alpha,10 beta-diol (1), 7 beta,13 alpha-diacetoxy-5 alpha-cinnamyloxy-2(3-->20)-abeo-taxa-4(20),11-diene-2 alpha,10 beta-diol (2), and 2 alpha,10 beta,13 alpha-triacetoxy-taxa-4(20),11-diene-5 alpha,7 beta,9 alpha-triol (3) respectively on the basis of 1D and 2D NMR data.