Selective oxidation-reduction and esterification of asiatic acid by Pestalotiopsis microspora and anti-HCV activity

Microbial transformation of asiatic acid (AA) by an endophytic fungus, Pestalotiopsis microspora, yielded six metabolites: 2-oxo-3β,15α,23-trihydroxyurs-12-ene-28-oic acid (1); 2-oxo-3β,15α,22α,23-tetrahydroxyurs-12-ene-28-oic acid (2); 2-oxo-3β,15α,23,30-tetrahydroxyurs-12-ene-28-oic acid (3); 2α,3β,15α,23,30-pentahydroxyurs-12-ene-28-oic acid methyl ester (4); 2α,3α,15α,23-tetrahydroxyurs-12-ene-28-oic acid (5); 2α,3α,15α,23,30-pentahydroxyurs-12-ene-28-oic acid (6). The structure elucidation of these products was confirmed based on the spectroscopic data. Compounds 2–6 were new. A possible biotransformation pathway is proposed. The anti-HCV activity of compounds 1–6 was also evaluated.     

Further triterpenoids and 13C NMR spectra of oleanane derivatives from Phytolacca acinosa

In addition to five known triterpenoids, namely acinosolic acid, phytolaccagenin, phytolaccagenic acid, esculentic acid and jaligonic acid, three new oleanane derivatives, designated as phytolaccagenin A, acinosolic acid A and acinosolic acid B, have been isolated and characterized from the defatted berries of Phytolacca acinosa. The new compounds have been identified as 3β-acetoxy-3β-methyloleanate-12-en-2β,23α-diol-28β-oic acid, 3β-acetoxy-28β-methyloleanate-12-en-2β-ol-30β-oic acid and 2β-acetoxy-28β-methyloleanate-12-en-3β-ol-30β-oic acid, respectively.     

Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (?)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain.     

New derivatives of ursolic acid through the biotransformation by Bacillus megaterium CGMCC 1.1741 as inhibitors on nitric oxide production

Microbial transformation of ursolic acid (1) by Bacillus megaterium CGMCC 1.1741 was investigated and yielded five metabolites identified as 3-oxo-urs-12-en-28-oic acid (2); 1β,11α-dihydroxy-3-oxo-urs-12-en-28-oic acid (3); 1β-hydroxy-3-oxo-urs-12-en-28, 13-lactoe (4); 1β,3β, 11α-trihydroxyurs-12-en-28-oic acid (5) and 1β,11α-dihydroxy-3-oxo-urs-12-en-28-O-β-d-glucopyranoside (6). Metabolites 3, 4, 5 and 6 were new natural products. Their nitric oxide (NO) production inhibitory activity was assessed in lipopolysaccharide (LPS) – stimulated RAW 264.7 cells. Compounds 3 and 4 exhibited significant activities with the IC₅₀ values of 1.243 and 1.711 μM, respectively. A primary structure-activity relationship was also discussed.     

The potential of Cyathus africanus for transformation of terpene substrates

The insecticidal sesquiterpenes cadina-4,10(15)-dien-3-one and aromadendr-1(10)-en-9-one were administered to the fungus Cyathus africanus ATCC 35853. Biotransformation of the former produced (4R)-9α-hydroxycadin-10(15)-en-3-one, while the latter gave 2β-hydroxyaromadendr-1(10)-en-9-one, 2α-hydroxyaromadendr-1(10)-en-9-one and 10α-hydroxy-1β,2β-epoxyaromadendran-9-one. The bioconversion of santonin led to the production of two analogues, 11,13-dihydroxysantonin and the hitherto unreported 8α,13-dihydroxysantonin, while cedrol yielded 3β,8β-dihydroxycedrane and 3α,8β-dihydroxycedrane. Stemod-12-ene, a diterpene, was transformed to 2-oxostemar-13-ene, a hitherto unknown analogue with a rearranged carbon framework. When methyl betulonate, a triterpenoid belonging to the lupane family, was supplied to the fungus 18α-ursane and 18α-oleanane derivatives, namely 19β-hydroxy-3-oxo-18α-oleanan-28-oic acid and 19α-hydroxy-3-oxo-18α-ursan-28-oic acids, were generated. There are no previous reports of fungal transformation of a triterpene in which a skeletal rearrangement occurred. All substrate administration experiments were done in the presence of the terpene cyclase inhibitor chlorocholine chloride (CCC), using the single phase – pulse feed method.     

Dammarane triterpenes from Cabralea canjerana (Vell.) Mart. (Meliaceae): Their chemosystematic significance

The stem of Cabralea canjerana (Vell.) Mart. yielded three new dammarane triterpenes 20S,24S-epoxy-7β,25-dihydroxy-3,4-secodammar-4(28)-en-3-oic acid, 20S,24S-epoxy-7β,15α,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid and 20S,24R-epoxy-7β,22ξ,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid, which were identified on the basis of spectroscopic methods. The known dammarane triterpenes ocotillone, eichlerianic acid, shoreic acid and the sterols sitosterol, campesterol, stigmasterol, sitostenone and stigmast-5-en-3-one were also isolated and identified. The branches yielded the above three known dammaranes and eichlerialactone. The dammaranes in C. canjerana display strong similarities with Trichilieae tribe, which contains several dammaranes. The data reported herein thus provide firm support for placing Cabralea within the subfamily Melioideae, Trichilieae tribe.     

Microbial transformation of ursolic acid by Syncephalastrum racemosum (Cohn) Schroter AS 3.264

Biotransformation of ursolic acid by the filamentous fungus Syncephalastrum racemosum (Cohn) Schroter AS 3.264 yielded five metabolites. Their structures were identified as 3β,21β-dihydroxy-urs-11-en-28-oic acid-13-lactone, 3β,7β,21β-trihydroxy-urs-11-en-28-oic acid-13-lactone, 1β,3β-dihydroxy-urs-12-en-21-one-28-oic acid, 1β,3β,21β-trihydroxy-urs-12-en-28-oic acid and 11,26-epoxy-3β,21β-dihydroxy-urs-12-en-28-oic acid based on NMR and MS spectroscopic analyses. The condensation reactions to form 28-oic acid-13-lactone ring and 11,26-epoxy ring are not frequently seen for the biotransformation of triterpenoids. One compound showed moderate inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).     

Triterpenoids from enkianthus campanulatus

From the leaves of Enkianthus campanulatus were isolated three new triterpenes, 3-oxo-19,23,24-trihydroxyurs-12-en-28-oic acid, 3β,6β, 19,23-tetrahydroxyurs-12-en-28-oic acid and 3β,6β,23-trihydroxyurs-12-en-28-oic acid.     

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.     

Narcissiflorine,narcissiflorinine and narcissifloridine,three triterpene saponins from Anemone narcissiflora

Narcissiflorine, narcissiflorinine and narcissifloridine, three new saponins, have been isolated from the ethanolic extract of Anemone narcissiflora (Ranunculaceae). The structural elucidation of narcissiflorine, narcissiflorinine and narcissifloridine has showed them to be [α-l-arabinofuranosyl-(1 → 4)-β-d-glucuronopyranosyl-(1→3)]- 3β-hydroxy-olean-12-en-28-oic acid, [α,-l-arabinofuranosyl-(1→2)-α-l-rhamnopyranosyl-(1→4)-β-d- glucuronypyranosyl(1→3)]-3-β-hydroxy-olean-12-en-28-oic acid and [α-l-arabinofuranosyl-(1→2)-α-l- rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→3)]-3-β-hydroxy-olean-12-en-28-oic acid, respectively.     

Triterpenoidal saponins of Pulsatilla koreana roots

Sixteen (1-16) triterpenoidal saponins were isolated from the roots of Pulsatilla koreana, of which four were determined as the previously unknown 23-hydroxy-3β-[(O-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (1), 23-hydroxy-3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl ester (2), 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (3), and 3β-[(O-α-L-rhamnopyranosyl-(1 → 2)-O-[β-D-glucopyranosyl-(1 → 4)]-α-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid 28-O-α-L-rhamnopyranosyl-(1 → 4)-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl ester (4), respectively, based on spectroscopic analysis. The inhibition of the lipopolysaccharide-induced nitric oxide production of sixteen isolated compounds was evaluated in RAW 264.7 cells at concentrations ranging from 1 μM to 100 μM.     

Two triterpenoid carboxylic acids from Acanthopanax trifoliatus

Two new triterpenoid carboxylic acids have been isolated from leaves of Acanthopanax trifoliatus and their structures elucidated as 3α, 11α-dihydroxylup-20(29)-en-28-oic acid and 30α, 11α,23-trihydroxylup-20(29)-en-28-oic acid by physical data and chemical transformations.     

A triterpene acid from Nepeta hindostana

A new triterpene acid has been isolated from alcoholic extract of Nepeta hindostana and its structure is elucidated as 2α,3β,23-trihydroxyurs-12-en-28-oic acid.     

Three new 18,19-seco-ursane glycosides from Elsholtzia bodinieri

Chromatographic separation of an extract of the aerial part of Elsholtzia bodinieri resulted in the isolation of three new 18,19-seco-ursane glycosides, bodiniosides E-G (1–3). Their structures were elucidated as 2α,12β,23-trihydroxy-3-(β-d-glucopyranosyl)-19-oxo-18,19-seco-urs-13(18)-en-28-O-β-d-glucopyranosyl ester (1), 3-β-d-glucopyranosyl-19-β-d-glucopyranosyl-12β,21-dihydroxy-18,19-seco-urs-13(18)-en-28-oic acid (2), and 2α,12β,21-trihydroxy-3-β-d-glucopyranosyl-19-β-d-glucopyranosyl-18,19-seco-urs-13(18)-en-28-oic acid (3), respectively, by extensive NMR techniques, including 1D- and 2D-NMR experiments, as well as comparing with spectral data with those of the known analogues.     

Triterpenoids of Terminalia sericea

The structures of sericic acid and sericoside, the major constituents of the roots of Terminalia sericea, have been determined. Sericic acid is 2α,3β,19α,24-tetrahydroxy-olean-12-en-28-oic acid and sericoside the corresponding C-28 D-glucosyl ester.     

Triterpenoid profile and bioactivity study of Oenothera maritima

Four new triterpenoids, 2α,3α,20β,23-tetrahydroxy-ursa-12,19(29)-dien-28-oic acid (1), 2α,3α,20β,23-tetrahydroxy-ursa-12,19(29)-dien-28,20β-lactone (2), 2α,3α-dihydroxy-ursa-12,19-dien-28-oic acid 28-O-β-d-glucopyranoside (3) and 2α,3α,23-trihydroxy-ursa-12,19(29)-dien-28-oic acid (4) together with six known compounds (5–10), were isolated from the aerial parts of Oenothera maritima Nutt. Their structures were elucidated on the basis of spectroscopic data and chemical methods. Compounds 1, 3–10 were evaluated for their in vitro thrombin inhibitory activity and their selectivity against factor Xa and trypsin.     

Arjunolitin,a triterpene glycoside fromTerminalia arjuna

Arjunolic acid diglycoside, which we have named arjunolitin, has earlier been reported fromTerminalia arjuna. Its structure has now been established as 3-O-β-d-glycopyranosyl 2α,3β-23-tri-hydroxyolean-12-en-28-oic acid 28-O-β-d-glucopyranoside by chemical and spectral data.     

3β-hydroxy-21β-e-cinnamoyloxyolean-12-en-28-oic acid,a triterpenoid from enterolobium contorstisiliquum

The triterpenes 3β-hydroxy-21β-E-cinnamoyloxyolean-12-en-20-oic acid, 3β,21β-dihydroxyolean-12-en-28-oic acid (machaerinic acid) and its lactone (3β-hydroxyolean-12-en-21β→28-lactone) were isolated from the fruits of Enterolobium contorstisiliquum. Methyl and ethyl esters of 3β,21β-dihydroxyolean-12-en-oic acid were isolated and characterized as artifacts. The structures of these triterpenes have been established by a study of their chemical and spectroscopic (IR, MS and NMR) data.     

New 19α-hydroxyursane-type triterpenes from the leaves of Meyna spinosa (= Vangueria spinosa), Rubiaceae

Two new 19α-hydroxyursane-type triterpenes, 2α,3α,19α,24,28-pentahydroxyurs-12-ene (1) and meyanthic acid, 3β-acetoxy-2β,19α,23-trihydroxyurs-12-en-28-oic acid (2) along with one new aliphatic ester, myricyl pentadecanoate (3) and five known compounds, 19α-hydroxyasiatic acid (4), oleanolic acid (5), myricyl alcohol (6), β-sitosterol (7) and its glycoside (8) were isolated from the methanolic leaf extract of Meyna spinosa Roxb. ex Link (= Vangueria spinosa Roxb., Rubiaceae). The structures of the new compounds were elucidated on the basis of extensive spectroscopic (including 2D NMR) analysis and comparison with literature. Except oleanolic acid, isolation of known compounds was reported for the first time from this plant.     

锐尖山香圆叶中三萜类成分的研究

从锐尖山香圆(Turpinia arguta (Lindl.) Seem.)叶中分离得到了11个三萜类化合物。通过光谱分析,分别鉴定其结构为熊果酸(1), 3β,6β,23-trihydroxy-12-oleanen-28-oic acid (2), 3β,6β,23-trihydroxyurs-12-en-28-oic acid (3), 3β,6β,19α,23-tetrahydroxyurs-12-en-28-oic acid (4), 1 α, 3β,23-trihydroxy-12-oleanen-28-oic acid (5), arjunglucoside II (6), rosamultin (7), 3β-O-β-D-glucopyranoylcincholic acid (8), cinchonaglycoside C (9), mussaendoside S (10) 和3β-O-β-D-glucopyranosyl quinovic acid 28-O-β-D-glucopyranosyl ester (11)。除化合物1和6,其它化合物均为首次从山香圆叶中分离得到。