Labdane diterpenes from an acacia species

Two new diterpenes, (13E)-labd-13-ene-3β,8α,15-triol and (13E)-3β,8α-dihydroxylabd-13-en-15-oic acid have been isolated from an unclassified Acacia sp. Chemical and spectroscopic evidence for their structure is presented. The known labdanes, sclareol, 13-epi-sclareol and (13E)-labd-13-ene-8α,15-diol were also isolated.     

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.     

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.     

Four new diterpenes from Sideritis serrata

Four new diterpenes have been isolated from Sideritis serata: lagascol (4, ent-8,5-friedopimar-5-ene-15S,16-diol), tobarrol (8, ent-15-beyerene-12α,17-diol), benuol (12, ent-15-beyerene-7α,17-diol) and serradiol (18, ent-16R-atis-13-ene-16,17-diol). The previously known diterpenes lagascatriol (1, ent-8,5-friedopimar-5-ene-11β,15S,16-triol), jativatriol (2, ent-15-beyerene-1β,12α,17-triol), conchitriol (3, ent-15-beyerene-7α,12α,17-triol) and sideritol (17, ent-16R-atis-13-ene-1β,16,17-triol) have also been obtained from the same source.     

Selective oxidation of steroidal allylic alcohols

Pyridinium chlorochromate in CH₂Cl₂ containing pyridine (2%) at 2—3°C has been found to effect the high yield selective oxidation of the hydroxyl function of a number of steroidal allylic alcohols. Under these conditions the oxidation of cholest-4-cn-3β-ol to the corresponding ketone was effected in 92% yield. Only the allylic hydroxyl function of 5α-cholest-8(14)-ene-3β,15α-diol, 5α-cholest-8(14)ene-3β,15β-diol and 5α-cholest-8(14)-ene-3β,7β-diol was oxidized under these conditions to give the corresponding α,β-unsaturated ketones in high yields. 5α-Cholest-8(14)-ene-3β,7α,15α-triol gave 5α-cholest-8(14)-ene-3β,7α-diol-15-one in 82% yield. Attempted oxidations of the 5α-cholestan-3β,15α-diol and 5α-cholest-7-ene-3β,15α-diol, both lacking an allylic hydroxyl function, under these conditions, were unsuccessful. Selective oxidation of the allylic alcohol function of 5α-cholest-8(14)-ene-3β,15β-diol using activated manganese dioxide gave 5α-cholest-8(14)-en-3β-ol-15-one in high yield while oxidation of the corresponding 15α-hydroxy epimer using manganese dioxide was unsuccessful.     

Labdane diterpenoids from Cistus ladaniferus

Three new diterpenic acids have been isolated from Cistus ladaniferus: 6,8(17) labdadien-15-oic, 7-oxo-8-labden-15-oic and 6β-acetoxy-7-oxo-8-labden-15-oic acids, beside labdanolic, 6-oxocativic,7α-hydroxy-8(17)-labden-15-oic, 8α-methoxy-labda-15-oic and 8α-hydroxy-13(E)-labden-15-oic acids.     

Two pentacyclic triterpenes from Rubia cordifolia

Rubicoumaric acid and rubifolic acid isolated from Rubia cordifolia have been shown to be 30-hydroxy-3β-p-hydroxycoumaryloxy-urs-12-ene-28-oic acid and 3β,30-dihydroxy-urs-12-ene-28-oic acid(30-hydroxyursolic acid) respectively on the basis of ¹H NMR, ¹³C NMR and mass spectral and chemical evidence.     

Differential metabolism of diastereoisomeric diterpenes by Preussia minima,found as endophytic fungus in Cupressus lusitanica

The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface sterilized stems of C. lusitanica. The ent-pimaradienoic acid was transformed into the known 7β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid, and into the novel diterpenes 7-oxo-8 β-hydroxy-ent-pimara-8(14)-15-dien-19-oic and 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acids. Isopimara-8(14)-15-dien-18-oic acid was converted into novel diterpenes 11α-hydroxyisopimara-8(14)-15-dien-18-oic acid, 7β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, and 1β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, along with the known 7β-hydroxyisopimara-8(14)-15-dien-18-oic acid. All compounds were isolated and fully characterized by 1D and 2D NMR, especially ¹³C NMR. The diterpene bioproduct 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid is an isomer of sphaeropsidin C, a phytotoxin that affects cypress trees produced by Shaeropsis sapinea, one of the main phytopathogen of Cupressus. The differential metabolism of the diterpene isomers used as substrates for biotransformation was interpreted with the help of computational molecular docking calculations, considering as target enzymes those of cytochrome P450 group.     

Two unsymmetric tetracyclic triterpenoids from cissus quadrangularis

Two new unsymmetric tetracyclic triterpenoids onocer-7-ene-3α,21β-diol and onocer-7-ene-3β,21α-diol together with sitosterol, δ-amyrin and δ-amyrone have been isolated from Cissus quadrangularis. The structures of the new compounds were elucidated on the basis of ¹H NMR, mass spectral and chemical evidence.     

尼泊尔水东哥的化学成分研究

从尼泊尔水东哥树皮的95%乙醇提取物中首次分离到12个化合物,应用波谱方法或与已知品对照的手段鉴定为auranamide(1)、aurantiamide benzoate(2)、齐墩果酸(3)、β-谷甾醇(4)、β-胡萝卜甙(5)、乌苏酸(6)、2α,3α-二羟基-12-烯-28-乌苏酸(7)、2α,3β,24-三羟基-12-烯-28-乌苏酸(8)、(2S,3S,4R,10E)-2-[(2′R)-2′-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol(9)、2α,3α,24-三羟基-12-烯-28-齐墩果酸(10)、2α,3β-二羟基-12-烯-28-乌苏酸(11)和2α,3α,24-三羟基-12-烯-28-乌苏酸(12)。     

Synthesis, aggregation behavior and cholesterol solubilization studies of 16-epi-pythocholic acid (3α,12α,16β-trihydroxy-5β-cholan-24-oic acid)

Synthesis, aggregation behavior and in vitro cholesterol solubilization studies of 16-epi-pythocholic acid (3α,12α,16β-trihydroxy-5β-cholan-24-oic acid, EPCA) are reported. The synthesis of this unnatural epimer of pythocholic acid (3α,12α,16α-trihydroxy-5β-cholan-24-oic acid, PCA) involves a series of simple and selective chemical transformations with an overall yield of 21% starting from readily available cholic acid (CA). The critical micellar concentration (CMC) of 16-epi-pythocholate in aqueous media was determined using pyrene as a fluorescent probe. In vitro cholesterol solubilization ability was evaluated using anhydrous cholesterol and results were compared with those of other natural di- and trihydroxy bile acids. These studies showed that 16-epi-pythocholic acid (16β-hydroxy-deoxycholic acid) behaves similar to cholic acid (CA) and avicholic acid (3α,7α,16α-trihydroxy-5β-cholan-24-oic acid, ACA) in its aggregation behavior and cholesterol dissolution properties.     

Diterpenes from Dysoxylum lukii Merr

Six new diterpenes and two known compounds were isolated from the stems of Dysoxylum lukii Merr and characterized on the basis of spectral data. Dysokusone F(1), 2-Oxoneoclerod-3, 13Z-dien-15-ol (2), 3α-(4-Hydroxy-3,5-dimethoxy-benzoyloxyl)-clerod-14-ene-4β,13-diol (3), 3α-(4-Hydroxybenzoyloxyl)-clerod-14-ene-4β,13-diol (4), and 3α-(4-Hydroxy-3-methoxybenzoyloxyl)-clerod-14-ene-4β,13-diol (5) exhibited inhibitory effects against PTP-1B with IC₅₀ values of 51.62±6.55, 56.74±7.96, 17.04±3.43, 28.96±4.59, and 19.70±2.57 μM, respectively.     

Caulophyllogenin: A novel triterpenoid from roots of Caulophyllum robustum

A new triterpenoid acid was isolated from Caulophyllum robustum roots. Its structure was proved to be 3β, 16α, 23-tri-hydroxy-olean-12-ene-28-oic acid.     

The structure and stereochemistry of a triterpene acid from lantana camara

The structure of lantoic acid, a new triterpene isolated from the leaves of Lantana camera, has been determined as 3,25-epoxy-3α,22β-dihydroxy-ursa-12-ene-28-oic acid by chemical and spectroscopic means.     

Biotransformation of ent-pimaradienoic acid by cell cultures of Aspergillus niger

Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent-pimaradienoic acid (1, PA, ent-pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30 °C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent-pimara-8(14),15-dien-19-oic acid (2), and three new derivatives, 1β-hydroxy ent-pimara-6,8(14),15-trien-19-oic acid (3), 1α,6β,14β-trihydroxy ent-pimara-7,15-dien-19-oic acid (4), and 1α,6β,7α,11α-tetrahydroxy ent-pimara-8(14),15-dien-19-oic acid (5), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation (2–5) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent-pimara-8(14),15-dien-19-oate (8), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure–activity relationship investigations.     

Diterpenoids of Halimium viscosum

From the neutral fraction of the hexane extract of Halimium viscosum the following components were isolated; 7-labdene-3β,l5-diol, 15-acetoxy-7-labden-3β-ol and a new diterpene-lactone with a rearranged ent-labdane skeleton, 13S-ent-9, 1-friedo-labd-1(10)-en-15-acetoxy-2R,18-olide. From the non-saponifiable part, beside 7-labdene-3β, 15-diol and 7, 13E-labdadiene-3β, 15-diol, the new diterpene 8(17)-labdene-3β, 7α, 15-triol was extracted. The structures were elucidated by spectroscopic methods, correlations or synthesis.     

Labdane diterpenoids from nolana rostrata

Six new labdane diterpenes, methyl 3-oxo-18-hydroxylabda-8(17),13E-dien-15-oate, methyl 2β,3β- dihydroxylabda-8(17),13E-dien-15-oate, 2-oxo-labda-8(17),13Z-dien-15-oic acid, 3-oxo-18-acetoxylabda-8(17),13Z- dien-15-oic acid, 3-oxo-18-hydroxylabda-8(17),13Z-dien-15-oic acid, 2β,3β-dihydroxylabda-8(17),13Z-dien-15-oic acid, and the known compound kaempferol-3,7,4′-trimethyl ether were isolated from the aerial parts of Nolana rostrata. The structures of the new compounds were elucidated by spectroscopic methods.     

Four new labdane diterpene oxides from Sideritis gomerae

Four new labdane diterpene oxides gomeraidehyde, 13-epigomeraldehyde, gomeric acid and 13-epigomeric acid as well as eperu-13-ene-8β,15-diol were isolated from the aerial part of Sideritis gomerae.     

Chemical syntheses of 5α-cholesta-6,8(14)-dien-3β-ol-15-one and related 15-oxygenated sterols

Hydroboration of 5α-cholesta-8,14-dien-3β-ol (I) gave 5α-cholest-8-en-3β,15α-diol (IV) in 89% yield. 5α-Cholest-7-en-3β,15α-diol (V) was prepared in 91% yield by hydroboration of 5α-cholesta-7,14-dien-3β-ol (II). Hydroboration of 27:63 mixture of I and II gave IV and V in 18% and 70% yields, respectively. 5α-Cholest-8-en-15α-ol-3-one and 5α-cholest-7-en-15α-ol-3-one were prepared in high yields from IV and V, respectively, by either selective oxidation with silver carbonate-celite or by enzymatic oxidation using cholesterol oxidase. 7α,8α-Epoxy-5α-cholestan-3β,15α-diol (VIII) was prepared in 93% yield by treatment of V with m-chloroperbenzoic acid. 5α-Cholest-8(14)-en-7α-ol-3,15-dione (IX) was prepared in 56% yield by oxidation of VIII with pyridinium chlorochromate followed by treatment of the crude product with acid. Compound IX was also obtained in 72% yield by selective chemical oxidation of 5α-cholest-8(14)-en-3β,7α,15α-triol. 5α-Cholesta-6,8(14)-dien-3,15-dione (X) was prepared in 89% yield by treatment of IX with p-toluenesulfonic acid under controlled conditions. Reduction of X with lithium tri-tert-butoxyaluminum hydride under controlled conditions gave 5α-cholesta-6,8(14)-dien-3β-ol-15-one in 84% yield.     

Biotransformation of dehydroepiandrosterone with Macrophomina phaseolina and β-glucuronidase inhibitory activity of transformed products

The biotransformation of dehydroepiandrosterone (1) with Macrophomina phaseolina was investigated. A total of eight metabolites were obtained which were characterized as androstane-3,17-dione (2), androst-4-ene-3,17-dione (3), androst-4-ene-17β-ol-3-one (4), androst-4,6-diene-17β-ol-3-one (5), androst-5-ene-3β,17β-diol (6), androst-4-ene-3β-ol-6,17-dione (7), androst-4-ene-3β,7β,17β?triol (8), and androst-5-ene-3β,7α,17β-triol (9). All the transformed products were screened for enzyme inhibition, among which four were found to inhibit the β-glucuronidase enzyme, while none inhibited the α-chymotrypsin enzyme.