Four new sesquiterpene polyol esters from Celastrus angulatus

Celastrus species, such as Celastrus angulatus, has been demonstrated to be very rich in natural sesquiterpene polyol esters sharing the β-dihydroagarofuran skeleton, some of which showed various biological activities. In this paper, four new sesquiterpene polyol esters, named as angulatins K-N (1–4), along with three known ones, 1β-acetoxy-9β-benzoxy-4α, 6α-dihydroxy-8α, 15-diisobutanoyloxy-2β-(α-methyl)-butanoyloxy-β-dihydroagarofuran, angulatin A, and celangulin III, were isolated from the root bark of C. angulatus. The structures of the new compounds were elucidated by extensive spectroscopic methods, mainly including HR-MS and 1D and 2D NMR techniques.     

Terpenoids and other constituents from Euphorbia bupleuroides

The phytochemical investigation of the roots of Euphorbia bupleuroides Desf. (Euphorbiaceae) yielded three new compounds named 4,20-dideoxy(4α)phorbol-12-benzoate-13-isobutyrate (1), 25-hydroperoxycycloart-3β-ol (2), and 3β,7β-dihydroxy-4α,14α-dimethyl-8β,9β-epoxy-5α-ergosta-24(28)-ene (3), together with 17 known compounds 4–20. Their structures were established from analysis of 1D (¹H, ¹³C and DEPT) and 2D NMR (COSY, HSQC, HMBC and NOESY) data, and of mass spectrometry (HRESIMS), and by comparison with literature data.     

Two new guaiane sesquiterpenes from Datura metel L. with anti-inflammatory activity

Chemical investigation of an acidic methanol extract of the whole plants of Datura metel resulted in the isolation of two new guainane sesquiterpenes, 1β,5α,7β-guaiane-4β,10α,11-triol (1) and 1α,5α,7α-11-guaiene-2α,3β,4α,10α,13-pentaol (2), along with eight known compounds: pterodontriol B (3), disciferitriol (4), scopolamine (5), kaempferol 3-O-β-d-glucosyl(1 → 2)-β-d-galactoside 7-O-β-d-glucoside (6), kaempferol 3-O-β-glucopyranosyl(1 → 2)-β-glucopyranoside-7-O-α-rhamnopyranoside (7), pinoresinol 4′′-O-β-d-glucopyranoside (8), (7R,8S,7′S,8′R)-4,9,4′,7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxy-lignan-4-O-β-d-glucopyranoside (9), and (7S,8R,7′S,8′S)-4,9,4′,7′-tetrahydroxy-3,3′-dimethoxy-7,9′-epoxylignan-4-O-β-d-glucopyranoside (10). Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR and MS spectra. Compounds 2-4 and 6-10 were shown to have modest anti-inflammatory effects through inhibition of NO production in LPS-stimulated BV cells.     

Metabolism of 5β-pregnane-3,20-dione and 3β-hydroxy-5β-pregnan-20-one by Digitalis suspension cultures

Digitalis purpurea normal callus suspension culture is capable of metabolizing 5β-pregnane-3,20-dione (1) to 3β-hydroxy-5β-pregnan-20-one (2), 3α-hydroxy-5β-pregnan-20-one (3), 3β-hydroxy-5β-pregnan-20-one glucoside (7) and 3α-hydroxy-5β-pregnan-20-one glucoside (8). Digitalis purpurea habituated callus suspension culture is also capable of metabolizing 1 to 2, 3, 5β-pregnane-3β,20β-diol (5), (7), (8), 5β-pregnane-3β,20α-diol monoglucoside (9) and 5β-pregnane-3α,20α-diol monoglucoside (11). Furthermore, it was observed that 3β-hydroxy-5β-pregnan-20-one (2) is converted to 7, 9 and 11 by both suspension cultures. At the same time, 1, 3, 5 and 8 were detected in normal callus, while 5β-pregnane-3β,20α-diol (4) and 5β-pregnane-3β,20β-diol monoglucoside (10) were present in the habituated callus culture.     

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.     

Microbial transformation of neoandrographolide by Mucor spinosus (AS 3.2450)

Microbial transformation of neoandrographolide (1), was performed by Mucor spinosus (AS 3.2450). Ten metabolites were obtained and identified as 14-deoxyandrographolide (2), 17,19-dihydroxy-8,13-ent-labdadien-16,15-olide (3), 3,14-dideoxyandrographolide (4), 7β-hydroxy-3,14-dideoxyandrographolide (5), 17,19-dihydroxy-7,13-ent-labdadien-16,15-olide (6), 8(17),13-ent-labdadien-16,15-olid-19-oic acid (7), 8α,17β-epoxy-3,14-dideoxyandrographolide (8), 8β,17,19-trihydroxy-ent-labd-13-en-16, 15-olide (9), phlogantholide-A (10), 19-[(β-d-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide (11) by spectroscopic and chemical means. Among them, products 3, 5, 6, 8 and 9 were characterized as new compounds. The inhibitory effects of compounds 1–11 on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated and their preliminary structure–activity relationships (SAR) were discussed.     

Phytochemical investigation of Eremostachys moluccelloides Bunge (Lamiaceae)

Phytochemical investigation of the aerial parts of Eremostachys moluccelloides Bunge led to the identification of a new diterpene, 2β,14-dihydroxy −11-formyl- 12-carboxy-13-des-isopropyl-13-hydroxymethyl-abieta-8,11,13- triene- 16(17)- lactone (1), along with the known compounds 12, 18-dicarboxy-14-hydroxy-13-des -isopropyl-13-hydroxymethyl- abieta-8,11,13-triene-16(17)-lactone (2), 5-hydroxy-3′,4′,7-trimethoxyflavone (3), 5-hydroxy-4’,7-dimethoxyflavone (4), luteolin-7-O-β-glucoside (5), verbascoside (6), luteolin 7-O-(6″-O-β-D-apiofuranosyl) -β-D-glucopyranoside (7), chlorogenic acid (8), echinacoside (9), apigenin-7-O-β-D-glucoside (10), p-coumaric acid (11), vanillic acid (12), apigenin-7-O-(6″-E-p-coumaroyl)-β-D-glucopyranoside (13), apigenin-7-O-(3″,6″-E-p-dicoumaroyl)-β-glucoside (14), lamalbide (15), 6β-hydroxy-7-epi-loganin (16), phloyoside II (17) The structures were elucidated on the basis of 1D and 2D NMR spectroscopy, UV, MS and by comparison with compounds previously reported in the literature. Compounds 1–4, 8, 9, 11, 12, 14 have not been reported previously from any species within the genus Eremostachys. Compounds 1–14, 17 were obtained from this species for the first time. The chemotaxonomic significance of the isolated compounds is discussed.     

Biotransformation of dianabol with the filamentous fungi and β-glucuronidase inhibitory activity of resulting metabolites

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2–6, while M. phaseolina transformed compound 1 into polar metabolites 7–11. These metabolites were identified as 6β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6β,12β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6β,15α,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17β-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7β,17β,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17β-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12–14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1–14 were evaluated for β-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of β-glucuronidase enzyme, with IC₅₀ values between 49.0 and 84.9 μM.     

Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi

Four new (1-4) and 13 known (5-17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4β-O-β-d-glucopyranoside (1), 4β,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4β,10β-dihydroxy-5α(H)-1, 11(13)-guaidien-8β,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8β,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC₅₀ values of 3.0-38.8 μg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).     

Sesquiterpenoids from Curcuma wenyujin with anti-influenza viral activities

Five sesquiterpenoids, 1α,8α-epidioxy-4α-hydroxy- 5αH-guai-7(11),9-dien- 12,8-olide. (1), 8,9-seco-4β-hydroxy-1α,5βH-7(11)-guaen-8,10-olide (2), 8α-hydroxy-1α, 4β,7βH-guai-10(15)-en- 5β,8β-endoxide(3), 7β,8α-dihydroxy-1α,4αH-guai-10(15)-en-5β,8β-endoxide(4) and 7-hydroxy-5(10),6,8-cadinatriene-4-one(5), together with seven known analogs were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were determined on the basis of spectroscopic methods including 2D NMR techniques, and the structures of 1 and 2 were confirmed by single-crystal X-ray diffraction experiment. Compounds 1–10 and 12 showed significant in vitro antiviral activity against the influenza virus A with IC₅₀ values ranged from 6.80 to 39.97 μM, and SI values ranged from 6.35 to 37.25.     

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.     

Four new lanostane-type triterpenoids from Inonotus obliquus

Four new lanostane-type triterpenoids, inonotsuoxodiol B (1), inonotsuoxodiol C (2), epoxyinonotsudiol (3), and methoxyinonotsutriol (4), were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be 3β,22R-dihydroxylanosta-9(11),24-dien-7-one (1), 3β,22R-dihydroxylanosta-7,24-dien-11-one (2), 9α,11α-epoxy-lanosta-7,24-diene-3β,22R-diol (3), and 7β-methoxylanosta-8,24-diene-3β,11α,22R-triol (4) on the basis of NMR spectroscopy, including 1D and 2D (¹H–¹H-COSY, NOESY, HMQC, HMBC) NMR spectra, and EIMS.     

Phenolic constituents from the roots of Rosa laevigata (Rosaceae)

Chemical investigation of the root of Rosa laevigata led to the isolation of sixteen phenolic compounds, including seven flavonoids (1–7), five condensed tannins (8–12), two stilbenes (13 and 14) and two benzoic acid derivatives (15 and 16). Their structures were identified as (+)-catechin (1), (+)-gallocatechin (2), (2R, 3S, 4S)-cis- leucocyanidin (3), (2R, 3S, 4S)-cis-leucofisetinidin (4), (2S, 3R, 4R)-cis- leucofisetinidin (5), dehydrodicatechin A (6), phloridzin (7), procyanidin B3 (8), fisetinidol-(4α, 8)-catechin (9), guibourtinidol- (4α, 8)-catechin (10), ent- isetinidol -(4α, 6)-catechin (11), fisetinidol-(4β, 8)-catechin (12), (Z)-3-methoxy-5-hydroxy- stilbene (13), (Z)-piceid (14), gallic acid (15) and 4-hydroxybenzoic acid- 4-O-β-D-glucopyranoside (16). Among them, compounds 3–7, 9–14, and 16 were isolated from R. laevigata for the first time, and compounds 3–7, 9, 10, 12–14 and 16 were reported for the first time from the genus Rosa. The chemotaxonomic significance of these compounds was summarized.     

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1?→?6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5–8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC₅₀ value of 15.41?μM.     

Synthesis,properties, and reactions of α- and β-D-glucopyranosyl esters of some tripeptides

The 2,3,4,6-tetra-O-benzyl-1-O-(N-benzyloxycarbonyltripeptidyl)-D-glucopyranoses 1, 8, and 13 were synthesised from 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose and the active esters of the appropriate N-protected tripeptides (Gly-Gly-Gly-, L-Phe-Gly-Gly-, and Gly-Gly-L-Phe-) in the presence of imidazole; the anomeric mixtures were resolved and the α and β anomers characterised. The β anomer of 13, containing the L and D enantiomers (ratio ≈ 3:1) of Gly-Gly-Phe- as the aglycon, could be resolved by column chromatography into the pure isomeric forms. Catalytic hydrogenolysis of the β anomers, in the presence and absence of a strong acid, yielded the free 1-esters 2β, 9β, and 14β, which were characterised as the monooxalate or trifluoroacetate salts and as free bases. Similarly, the α anomers afforded 2α, 9α, and 14α, whereas omission of the strong acid led to accompanying 1→2 acyl migration, to give the 2-O-acyl derivatives. All of the compounds prepared were converted into the N-acetyl and/or peracetylated derivatives. The 1-esters 2β and 9β, both in the charged and uncharged form, and the trifluoroacetate salt of 14β, are susceptible to cleavage by β-D-glucosidase; the enzyme had no effect on the uncharged form of 14β. This difference between 14β and its salt is discussed in conformational terms.     

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).     

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.     

Two new flavonols,including one flavan dimer,from the roots of Indigofera stachyodes

A new flavan dimer, 2α,3α-epoxyflavan-5,7,3′,4′-tetraol-(4β→8)-flavan-5′′,7′′,4′′′-triol (1), and a new flavonol, 3-O-(3-nitropropanoyl)-2,3-cis-5,7,3′,4′-tetrahydroxyflavan (2), together with a known compound, 2α,3α-epoxy-5,7,3′,4′-tetrahydroxyflavan-(4β→8)-epicatechin (3), were isolated from the roots of Indigofera stachyodes. Their structures were elucidated by spectroscopic techniques including MS, 1D NMR, and 2D NMR. Compounds 2 and 3 were evaluated to determine their protective effects against carbon tetrachloride (CCl₄)-induced hepatotoxicity in the human liver cell line HL-7702. The results showed that 2 and 3 could protect HL-7702 cells from injury induced by CCl₄, with cell survival rates of 122.0% and 72.5%, respectively.     

Two new cyclohexylethanol derivatives from the whole plants of Incarvillea delavayi and their inhibition on LPS-induced NO release in BV-2 cells

Delavatones A (4β, 7α-dihydroxy-7β-(13-methylpent-11-one-12-ene)-octahydrobenzofuran, 1) and B (4β, 7α-dihydroxy-7β-(propan-9-one)-octahydrobenzofuran, 2), two structurally unique cyclohexylethanol derivatives with a substituted alkyl chain, were isolated from the 90% ethanol extract of the whole plants of Incarvillea delavayi. The structures of delavatones A and B were characterized by the interpretation of 1D and 2D NMR spectroscopic data in combination with NMR chemical shift calculation coupled with DP4+ probability analysis. In an in vitro assay for anti-inflammatory effect, delavatones A and B displayed remarkable suppression on NO production in LPS-induced BV-2 cells at concentrations ranging from 6 μM to 100 μM.     

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.