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.     

Viscidic acid A and B,two ent-labdane derivatives from Chrysothamnus viscidiflorus

The chemical investigation of Chrysothamnus viscidiflorus afforded, in addition to known bisabolene derivatives, elemicin and p-hydroxyacetophenone, two new diterpene acids. Their structures were determined, by spectroscopic methods and some chemical transformations, as ent-labd-8(17),13E-dien-15-ol-18-oic acid (viscidic acid A) and ent-labd-8(17),13E-dien-15-acetoxy-18-oic acid (visidic acid B).     

Diterpenoids and a sesquiterpene lactone from viguiera ladibractate

Eight known diterpene acids, ent-12-oxokaur-9(11),16-dien-19-oic acid, ent-12β-hydroxykaur-9(11),16-dien-19-oic acid, ent-isokaur-15(16)-en-17,19-dioic acid, ent-15α,16-epoxy-17-hydroxykaura-19-oic acid, ent-kaura-17,19-dioic acid, ent-kaur-16-en-19-oic acid, grandifloric acid, angeloyloxygrandifloric acid, as well as a new sesquiterpene lactone, ladibranolide, were isolated from Viguiera ladibractate. The stereochemistry of the sesquiterpene lactone was established by NOE experiments.     

Seven new triterpenoids from the aerial parts of Ilex cornuta and protective effects against H2O2-induced myocardial cell injury

Seven new triterpenoids (1–7), together with two known ones (8–9), were isolated from the aerial parts ofIlex cornuta. The leaves of I. cornuta are the major source of “Kudingcha”, a popular herbal tea consumed in China and other countries. The structures of compounds 1–7 were determined as 20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (1), 20-epi-urs-12,18-dien-28-oic acid 2′-O-acetyl-3β-O-α-l-arabinopyranoside (2), 20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (3), 3β,23-dihydroxy-20-epi-urs-12,18-dien-28-oic acid (4), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-α-l-arabinopyranoside (5), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronic acid (6), 23-hydroxy-20-epi-urs-12,18-dien-28-oic acid 3β-O-β-d-glucuronopyranoside-6-O-methyl ester (7), on the basis of spectroscopic analyses (IR, ESI–MS, HR-ESI–MS, 1D and 2D NMR) and chemical reactions. Protective effects against H₂O₂-induced H9c2 cardiomyocyte injury were tested in vitro for compounds 1–9, and the data showed that compound 4 had significant cell-protective effect. Compounds 1-9 did not show significant DPPH radical scavenging activity.     

New guaiane sesquiterpenes from Artemisia rupestris and their inhibitory effects on nitric oxide production

Phytochemical investigation of the ethanol extract of the aerial parts of Artemisia rupestris resulted in the isolation of three new guaiane sesquiterpenes, (1R,7R,10S)-1-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (1), (1R,7R,10S)-10-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (2), pechueloic acid 12-O-β-d-glucopyranoside (3), together with 12 known compounds (4–15). The structures of these new compounds were established on the basis of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. All isolates were evaluated for their in vitro inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells, and the structure–activity relationships were also discussed.     

Terpenes with antimicrobial activity from Cretan propolis

Five terpenes, the diterpenes: 14,15-dinor-13-oxo-8(17)-labden-19-oic acid and a mixture of labda-8(17),13E-dien-19-carboxy-15-yl oleate and palmitate as well as the triterpenes, 3,4-seco-cycloart-12-hydroxy-4(28),24-dien-3-oic acid and cycloart-3,7-dihydroxy-24-en-28-oic acid were isolated from Cretan propolis. Moreover, 18 known compounds were also isolated, seven of them for the first time as propolis components. All structures were established on the basis of spectroscopic analysis and chemical evidence. All isolated compounds were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria as well as against some human pathogenic fungi showing a broad spectrum of antimicrobial activity.     

(25S)-Cholesten-26-oic acid derivatives from an Indonesian soft coral Minabea sp.

(25S)-3-Oxocholesta-1,4-dien-26-oic acid (1) and a new (25S)-18-acetoxy-3-oxocholesta-1,4-dien-26-oic acid (2) were isolated from a soft coral Minabea sp. (cf. aldersladei) collected in North Sulawesi, Indonesia, together with two known cholic-acid-type compounds, 3-oxochol-1,4-dien-24-oic acid (3) and 3-oxochol-4-en-24-oic acid (4). The structures of these compounds were determined on the basis of their spectroscopic data. The absolute stereochemistry at C-25 of 2 was determined by comparative ¹H NMR study using chiral anisotropic reagents [(S)- and (R)-phenylglycine methyl esters]. This is the first to report compound 1 as a natural product.     

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。     

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.     

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.     

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.     

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.     

Cadinane-type sesquiterpenoids from Schisandra bicolor

The phytochemical investigation on the stems of Schisandra bicolor led to the isolation of seven cadinane-type sesquiterpenoids, 2-hydroxy-11,12-dehydrocalamenene (1), ent-T-muurolol (2), (+)-ent-epicubenol (3), (1S,4S)-7,8-dihydroxy-11,12-dehydrocalamenene (4), cadinane-T-cadinol (5), (−)-cadin-4,10(15)-dien-11-oic acid (6), and cadina-4,10(15)-dien-3-one (7). Their structures were determined by extensive analysis of their spectroscopic data. All the isolates were isolated from this species for the first time. The chemotaxonomic significance of these compounds was also summarized.     

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.     

翠柏二萜类成分及其抗炎活性研究

采用正相硅胶、MCI、反相RP-18和半制备液相等色谱技术,对柏科翠柏属植物翠柏(Calocedrus macrolepis)中的二萜类成分及其抗炎活性进行了研究。结果表明:从中共分离得到8个二萜类化合物,分别鉴定为8-hydroxy-labda-13(16),14-dien-19-yl trans-coumarate(1)、trans-communal(2)、trans-communic acid(3)、pinusolidic acid(4)、isocupressic acid(5)、fokihodgin F(6)、acetylisocupressic acid(7)、15,16-dihydroxy-labda-8(17),13(E)-dien-19-oic acid(8)。化合物1~8均为首次从该植物中分离得到。化合物7对LPS诱导的RAW264.7巨噬细胞释放NO具有显著的抑制作用,其IC50值为9.31μmol·L~(-1)。     

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.     

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.     

Diterpenoids from Sideritis varoi subspecies cuatrecasasii: 13C NMR of ent-13-epi-manoyl oxides functionalized at C-12

Several ent-13-epi-manoyl oxides and a new natural product, ent-8α-hydroxylabda-13(16),14-dien-19-oic acid, have been isolated from Sideritis varoi subsp. cuatrecasasii. In addition, a study has been made of some natural and semisynthetic ent-13-epi-manoyl oxides functionalized at C-12.     

Beckmann rearrangement products of methyl 3-oxo-tirucall-8, 24-dien-21-oate from Boswellia serrata gum and their anti-tumor activity

3-Oxo-tirucall-8, 24-dien-3-one-21-oic acid is a minor natural product isolated from Boswellia serrata gum apart from β-boswellic acids. Since oxidation of 3-hydroxy group of β-boswellic acids leads to unstable beta-keto acids, Beckmann rearrangement could not be tried. Hence A-ring modified 3-oxo-tirucall-8, 24-dien-21 methyl esters (2–6) were synthesized for the first time via Beckmann rearrangement and evaluated for their anticancer potential against five human cancer cell lines (MCF-7, SW-982, HeLa, PC-3 and IMR-132) by MTT assay. While naturally occurring 3-oxo-tirucallic acid (1) and its methyl ester (2) exhibited nearly the same antiproliferative activity, A-ring modified molecules displayed improved anti-tumor activity with methyl A-homo-4-aza-3-oxo-tirucall-8, 24, dien-3-one-21-oate (4) exhibiting significant effect against prostate cancer cell lines.     

Clerodane diterpenes from Aristolochia species

The investigation of Aristolochia brasiliensis and A. esperanzae afforded 12 clerodane derivatives, including the following six novel ones: rel (5S, 8R, 9S, 10R)-2-oxo-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-2-oxo-ent-clerod-3,13-dien-15-oic acid methyl ester, (5R, 8R, 9S, 10R)-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-ent-clerod-3,13-dien-15-oic acid, (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-3-cleroden-15-oic acid methyl ester and (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-clerod-3,13-dien-15-oic acid methyl ester. The structures were assigned on the basis of spectral data and derivatization by chemical reactions. The occurrence of this type of diterpene has not previously been reported in Aristolochiaceae.