Hopane triterpenes as chemotaxonomic markers for the scale insect pathogens Hypocrella s. lat. and Aschersonia

The scale insect pathogens Hypocrella s. lat. and their Aschersonia anamorphs, collected at various locations in Thailand, were surveyed for their productivity of three hopane triterpenes, zeorin (6α,22-dihydroxyhopane), dustanin (15α,22-dihydroxyhopane), and 3β-acetoxy-15α,22-dihydroxyhopane, when cultured in a liquid medium (potato-dextrose broth) under static conditions. Among 53 strains of Aschersonia species, 48 strains (91 %) produced at least one of these compounds. Hypocrella and Moelleriella species (43 strains) also frequently produced these triterpenoids; only two strains lacked all of these triterpenes. The results demonstrate that hopane triterpenes may be suitable for use as chemotaxonomic markers for Hypocrella and Moelleriella species and their Aschersonia anamorphs.     

Eudesmane-type sesquiterpenes from the liverwort Apomarsupella revolute

Phytochemical investigation of the Et₂O extract of liverwort Apomarsupella revolute led to isolation and identification of five new eudesmane-type sesquiterpenoids, 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien (1), 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien-3-one (2), 5α,6β-dihydroxy-9β-acetoxy-eudesma-4(15),11-dien (3) 4β-hydroxy-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (4) and 4β-methox-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (5), two of which were trinorsesquiterpenoids. Their structures were established unequivocally on the basis of spectroscopic data analysis. All compounds were preliminary bioscreened for their cytotoxicities and antifungal activities.     

(22<Emphasis Type="Italic">R</Emphasis>,23<Emphasis Type="Italic">R</Emphasis>)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one: Improved synthesis and toxicity to MCF-7 cells

The chemical synthesis of (22R,23R)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one from (22A)-3β-acetoxy-5α-ergosta-7,14,22-triene was improved. The stages of obtaining and isomerization of (22A)-3β-acetoxy-14α15α-epoxy-5α-ergosta-7,22-diene were optimized. The introduction of (22R,23R)-epoxide cycle was carried out by alkaline treatment of intermediate (22S,23R)-3β,23-diacetoxy-22-iodo-5α-ergost-8(14)-en-15-one. In cells of human breast carcinoma MCF-7, (22R,23R)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one showed a high toxicity (TC₅₀ = 0.4±0.1 μM at 48-h incubation in serum-free medium).     

Cycloartane glycosides from Astragalus gombo

Six new cycloartane-type triterpene glycosides named 3-O-[β-d-glucopyranosyl(1 → 2)-β-d-xylopyranosyl]-3β,16β,23(R),24(R),25-pentahydroxycycloartane (1), 3-O-[β-d-glucopyranosyl(1 → 2)-β-d-xylopyranosyl]-3β,16β,23(R),24(R)-tetrahydroxy-25-dehydrocycloartane (2), 3-O-[β-d-xylopyranosyl]-6α-acetoxy-23α-methoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (3), 3-O-[β-d-xylopyranosyl]-6α-acetoxy-23α-butoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (4), 3-O-[β-d-glucopyranosyl(1 → 2)]-β-d-xylopyranosyl]-6α-acetoxy-23α-methoxy-16β,23(R)-epoxy-24,25,26,27-tetranorcycloartane (5), 3-O-[β-d-glucopyranosyl(1 → 2)]-β-d-xylopyranosyl]-23α-methoxy-16β,23(R)-epoxy-4,25,26,27-tetranorcycloartane (6), in addition to three known secondary metabolites consisting of another cycloartane triterpene glycoside and two flavonol glycosides, were isolated from the aerial parts of Astragalus gombo Coss. & Dur. (Fabaceae). The structures of the isolated compounds were established by spectroscopic methods, including 1D and 2D-NMR, mass spectrometry and comparison with literature data.     

Eudesmane sesquiterpenoid lactones and abietane diterpenoids from Ajuga forrestii Diels

Four eudesmane sesquiterpenoid lactones (1–4) and seven abietane diterpenoids (5–11) were isolated from the whole plants of Ajuga forrestii. Among them, 3α-acetoxy-1α,8β-dihydroxyeudesm-7(11)-en-8,12-olide (1), 3α-acetoxy-1α-hydroxyl-eudesm-8,7(11)-dien-8,12-olide (2), 1α-acetoxy-8α-oxyethyl-2-oxo-eudesman-3,7(11)-dien-8,12-olide (3) and 2α,3β,11,12-tetrahydroxy-7β,20-epoxy-8,11,13-abietatriene (11) are novel compounds. The structures of compounds 1–11 were determined by spectroscopic analysis. Compound 2 exhibited weak cytotoxicity on HepG2 and MCF-7 cell lines.     

Microbial transformation of acetyl-11-keto-β-boswellic acid and their inhibitory activity on LPS-induced NO production

The capabilities of 20 strains of fungi to transform acetyl-11-keto-β-boswellic (AKBA) were screened. And biotransformation of AKBA by Cunninghamella blakesleana AS 3.970 afforded five metabolites (1–5), while two metabolites (6, 7) were isolated from biotransformation of Cunninghamella elegans AS 3.1207. The chemical structures of these metabolites were identified by spectral methods including 2D NMR and their structures were elucidated as 7β-hydroxy-3-acety-11-keto-β-boswellic acid (1), 21β-dihydroxy-3-acety-11-keto-β-boswellic acid (2), 7β,22α-dihydroxy-3-acety-11-keto-β-boswellic acid (3), 7β,16α-dihydroxy-3-acety-11-keto-β-boswellic acid (4), 7β,15α-dihydroxy-3-acety-11-keto-β-boswellic acid (5); 7β,15α,21β-trihydroxy-3-acety-11-keto-β-boswellic acid (6) and 15α,21β-dihydroxy-3-acety-11-keto-β-boswellic acid (7). All these products are previously unknown. Their primary structure–activity relationships (SAR) of inhibition activity on LPS-induced NO production in RAW 264.7 macrophage cells were evaluated.     

Three new dihydroagarofuran sesquiterpenoids from Celastrus orbiculatus

Three new β-dihydroagarofuran sesquiterpene polyesters, 1β-acetoxy-8α,9β-dibenzoyloxy-13-nicotinoyloxy-β-dihydroagarofuran (1), 1β,2β-diacetoxy-9α-benzoyloxy-13-nicotinoyloxy-β-dihydroagarofuran (2), and 6α,8α,9β,13-tetraacetoxy-1β-cinnamoyloxy-2β,4α-dihydroxy-β-dihydroagarofuran (3) were isolated from the fruits of Celastrus orbiculatus Thunb. Their structures were determined by means of extensive spectroscopic analyses (IR, ESIMS, HRESIMS, 1D and 2D NMR).     

Zierane sesquiterpene lactone,cembrane and fusicoccane diterpenoids,from the Tahitian liverwort Chandonanthus hirtellus

Cembrane-type diterpenoids, 13,18,20-epi-iso-chandonanthone (1) and (8E)-4α-acetoxy-12α,13α-epoxycembra-1(15),8-diene (2), two fusicoccane-type diterpenoids, fusicoauritone 6α-methyl ether (3) and 6β,10β-epoxy-5β-hydroxyfusicocc-2-ene (4) and a zierane sesquiterpene γ-lactone, chandolide (5) were isolated from the Tahitian liverwort Chandonanthus hirtellus (Web.) Mitt., together with eight known diterpenoids, chandonanthine (6), fusicogigantone A (7), fusicogigantone B (8), fusicogigantepoxide (9), anadensin (10), fusicoauritone (11), ent-verticillol (12) and ent-epi-verticillol (13). Their structures were established by a combination of extensive NMR spectroscopy and/or X-ray crystallographic analyses. Compounds 1, 5 and 10 showed weak cytotoxic activity against HL-60. Compound 3 also indicated weak cytotoxic activity against KB cell lines.     

An antibacterial cytochalasin derivative from the marine-derived fungus Diaporthaceae sp. PSU-SP2/4

A new pentacyclic cytochalasin (diaporthalasin, 1) and a new ethyl trihydroxytridecatrienoate (diaporthacol, 2) together with five known compounds, R-mevalonolactone (4), dothiorelone C (5), (4S,7S,13S)-4,7-dihydroxy-1,3-tetradeca-1,5-dienolide (6), 4β-acetoxy-9β,10β,15α-trihydroxyprobotrydial (7) and O-methyldihydrobotrydial (8) were isolated from the marine-derived fungus Diaporthaceae sp. PSU-SP2/4. The structures were established by spectroscopic techniques. Compound 1 displayed significant antibacterial activity against both Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 2 μg/mL.     

Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var. camerunensis

Phytochemical investigation of the seeds of Salacia longipes var. camerunensis led to the isolation of four sesquiterpenoid derivatives, salaterpene A (1) (1α,2β,8β-triacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene B (2) (1α,2β,8β-triacetoxy-9β-benzoyloxy-6β-cinnamoyloxy-4β-hydroxy-dihydro-β-agarofuran), salaterpene C (3) (1α,2β-diacetoxy-6β,9β-dibenzoyloxy-4β-hydroxy-dihydro-β-agarofuran) and salaterpene D (4) (2β-acetoxy-1α,6β-dibenzoyloxy-4β-hydroxy-9β-nicotinoyloxy-dihydro-β-agarofuran) together with two known compounds (5 and 6). The structures of the compounds were established by means of NMR spectroscopy. Compounds 1–4 and 6 were tested in vitro for their antiplasmodial activity against Plasmodium falciparum chloroquine-resistant strain W2. All the tested compounds exhibited a moderate potency with IC₅₀ below 2.7 μM.     

Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii

Strophasterols E (1) and F (2) were isolated from the fruiting bodies of Pleurotus eryngii, together with four new ergostane-type sterols (3–6). Single-crystal X-ray diffraction analysis performed on the tris-p-bromobenzoate derivatives of compounds 1 and 2 allowed these two compounds to be identified as the structurally rare (22S,23R)- and (22S,23S)-5α,6α-epoxy-3β,7β,23-trihydroxy-15(14 → 22)-abeo-ergost-8-en-14-one, respectively. The inhibitory effects on nitric oxide production of the six new steroids thus isolated from the fruiting bodies of P. eryngii were also evaluated.     

Renoprotective chemical constituents from an edible mushroom,Pleurotus cornucopiae in cisplatin-induced nephrotoxicity

Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10 μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.     

Khayanolides from African mahogany Khaya senegalensis (Meliaceae): A revision

Five khayanolides (1-O-acetylkhayanolide B 1, khayanolide B 2, khayanolide E 3, 1-O-deacetylkhayanolide E 4, 6-dehydroxylkhayanolide E 5) were isolated from the stem bark of African mahogany Khaya senegalensis (Meliaceae). Their structures and absolute configurations were determined through extensive spectroscopic analyses including MS, NMR, and single-crystal X-ray diffraction experiments. The results established that two previously reported khayanolides, 1α-acetoxy-2β,3α,6,8α,14β-pentahydroxy-[4.2.1^10,30.1^1,4]-tricyclomeliac-7-oate 6 and 1α,2β,3α,6,8α,14β-hexahydroxy-[4.2.1^10,30.1^1,4]-tricyclomeliac-7-oate 7, were, in fact, 1-O-acetylkhayanolide B 1 and khayanolide B 2, and that the two reported phragmalin derivatives, methyl 1α-acetoxy-6,8α,14β,30β-tetrahydroxy-3-oxo-[3.3.1^10,2.1^1,4]-tricyclomeliac-7-oate 8 and methyl 1α,6,8α,14β,30β-pentahydroxy-3-oxo-[3.3.1^10,2.1^1,4]-tricyclomeliac-7-oate 9, were, in fact, khayanolide E 3 and 1-O-deacetylkhayanolide E 4, respectively. Based on the results from this study and consideration of the biogenetic pathway, the methyl 6-hydroxyangolensate in African mahogany K. senegalensis should have a C-6 S configuration while methyl 6-hydroxyangolensate in genuine mahogany Swietenia species should have a C-6 R configuration.     

The withanolides of Withania somnifera chemotypes I and II

Seven steroidal lactones of the withanolide series have been isolated as minor constituents of the leaves of Withania somnifera Dun. (Solanaceae) chemotype I, along with the major component withaferin A. Structures have been assigned to the new compounds: withanolide N (17α,27-dihydroxy-1-oxo-20R,22R-witha-2,5,14,24-tetraenolide) (6a) and withanolide O (4β,17α-dihydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide) (7a). Similarly the leaves of W. somnifera chemotype II afforded three new withanolides along with the major component withanolide D (9a) and trace amounts of withanolide G (10). The new compounds are: 27-hydroxywithanolide D(4β,20α,27-trihydroxy-1-oxo-5β,6β-epoxy-20R,22R-witha-2,24-dienolide) (11a), 14α-hydroxywithanolide D (4β,14α,20α-trihydroxy-1-oxo-5β,6β-epoxy-20R,22R-witha-2,24-dienolide) (12a) and 17α-hydroxywithanolide D (4β,17β,20α-trihydroxy-1-oxo-5β,6β-epoxy-20S,22R-witha-2,24-dienolide) (13a). Whereas all the withanolides of chemotype I are unsubstituted at C-20 (20α-H), those of chemotype II possess an OH at this position (20α-OH).     

New 9,19-cycloartenol glycosides isolated from the roots of Cimicifuga simplex and their anti-inflammatory effects

Two new cycloartenol triterpene saponins, 3β,16α-dihydroxy-12-acetoxy-16,22-cyclo-23-ketone-24R,25-epoxy-cycloartane-3-O-β-d-galactopyranoside (1), 3β,16α-dihydroxy-12-acetoxy-16,22-cyclo-23-ketone-24R,25-epoxy-cycloartane-7-ene-3-O-β-d-xylopyranoside (2), were isolated from the ethyl acetate soluble fraction of the roots of Cimicifuga simplex Wormsk. Their structures were established by detailed spectroscopic analysis, including extensive 2D NMR data. Their anti-proinflammatory activities were also carried out by LPS-stimulated IL-6, IL-23 and TNF-α genes expression in RAW cells in vitro using Q-PCR method.     

Steroidal constituents of Solanum xanthocarpum

From the extract of the fruits of Solanum xanthocarpum (Solanaceae), five new steroidal compounds were isolated and characterized: 4α-methyl-24ξ-ethyl-5α-cholest-7-en-3β,22ξ-diol (1), 3β,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (2), 3β-benzoxy-14β,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (3), 3β-benzoxy-14α,22ξ-dihydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (4) and 3β-(p-hydroxy)-benzoxy-22ξ-hydroxy-4α-methyl-24ξ-ethyl-5α-cholest-7-en-6-one (5).     

Alkenylresorcinols and cytotoxic activity of the constituents isolated from Labisia pumila

Phytochemical investigation on the leaves of Labisia pumila (Myrsinaceae), an important medicinal herb in Malaysia, has led to the isolation of 1-O-methyl-6-acetoxy-5-(pentadec-10Z-enyl)resorcinol (1), labisiaquinone A (2) and labisiaquinone B (3). Along with these, 16 known compounds including 1-O-methyl-6-acetoxy-5-pentadecylresorcinol (4), 5-(pentadec-10Z-enyl)resorcinol (5), 5-(pentadecyl)resorcinol (6), (−)-loliolide (7), stigmasterol (8), 4-hydroxyphenylethylamine (9), 3,4,5-trihydroxybenzoic acid (10), 3,4-dihydroxybenzoic acid (11), (+)-catechin (12), (−)-epicatechin (13), kaempferol-3-O-α-rhamnopyranosyl-7-O-β-glycopyranoside (14), kaempferol-4′-O-β-glycopyranoside (15), quercetin-3-O-α-rhamnopyranoside (16), kaempferol-3-O-α-rhamnopyranoside (17), (9Z,12Z)-octadeca-9,12-dienoic acid (18) and stigmasterol-3-O-β-glycopyranoside (19) were also isolated. The structures of these compounds were established on the basis of 1D and 2D NMR spectroscopy techniques (¹H, ¹³C, COSY, HSQC, NOESY and HMBC experiments), mass spectrometry and chemical derivatization. Among the constituents tested 1 and 4 exhibited strongest cytotoxic activity against the PC3, HCT116 and MCF-7 cell lines (IC₅₀ values ⩽10 μM), and they showed selectivity towards the first two-cell lines relative to the last one.     

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.     

Inhibitors of sterol biosynthesis. Syntheses of 14α-alkyl substituted 15-oxygenated sterols

The chemical syntheses of a number of 14α-alkyl substituted 15-oxygenated sterols have been pursued to permit evaluation of their activity in the inhibition of the biosynthesis of cholesterol and other biological effects. Described herein are the first chemical syntheses of 14α-ethyl-5α-cholest-7-en-3β-ol-15-one, bis-3β,15α-acetoxy-14α-ethyl-5α-cholest-7-ene, 3β-acetoxy-14α-ethyl-5α-cholest-7-en-15β-ol, 14α-ethyl-5α-cholest-7-en-3β,15β-diol, 14α-ethyl-5α-cholest-7-en-3β,15α-diol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15α-ol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15β-ol, bis-3β,15α-hexadecanoyloxy-14α-ethyl-5α-cholest-7-ene, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 3α-benzoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 14α-ethyl-5α-cholest-7-en-3α-ol-15-one, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl potassium sulfate (monohydrate), 14α-ethyl-5α-cholest-7-en-15-on-3α-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3α-yl potassium sulfate (monohydrate), 3β-ethoxy-14α-ethyl-5α-cholest-7-en-15-one, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15-one, 14α-n-propyl-5α-cholest-7-en-3β-ol-15-one, bis-3β, 15α-acetoxy-14α-n-propyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15β-ol, 14α-n-propyl-5α-cholest-7-en-3β, 15α-diol, 14α-n-propyl-5α-cholest-7-en-3β, 15β-diol, 14α-n-butyl-5α-cholest-7-en-3β-ol-15-one, 3β-acetoxy-14-α-n-butyl-5α-cholest-7-en-15-one, bis-3β,15α-acetoxy-14α-n-butyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-butyl-5α-cholest-7-en-15β-ol, 14α-n-butyl-5β-cholest-7-en-3β, 15β-diol, and 14α-n-butyl-5α-cholest-7-en-3β, 15α-diol.