Triterpenoid saponins from Campsiandra guayanensis

Thirteen new triterpenoid saponins (1-13) were isolated from the aerial parts of Campsiandra guayanensis. Their structures were elucidated by 1D and 2D NMR experiments including 1D-TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The aglycon moieties of 1-10 were assigned as oleanane derivatives and those of 11-13 as lupane derivatives.     

Kopetdaghins A-E, sesquiterpene derivatives from the aerial parts and the roots of Dorema kopetdaghense

Three new sesquiterpene derivatives, kopetdaghins A-C (1-3), one known prenylated coumarin (7), and two known steroid glucosides, sitosterol 3-O-glucoside and stigmasterol 3-O-glucoside, were isolated from the aerial parts of Dorema kopetdaghense. In addition, two new sesquiterpene derivatives, kopetdaghin D (4) and kopetdaghin E (5), together with kopetdaghins A-C and one known sesquiterpene coumarin (6), were isolated from the roots of the plant. The structures of these compounds were elucidated by various 1D and 2D NMR techniques as well as high-resolution positive-ion ESIMS.     

Further labdane and kaurane diterpenoids and other constituents from Plectranthus fruticosus

Eight new diterpenoids, one labdane and seven kaurane derivatives, and a new aromadendrane-type sesquiterpenoid have been isolated from the most polar chromatographic fractions of an acetone extract of Plectranthus fruticosus. The structures of the new compounds (1-9) were established mainly by 1D and 2D NMR studies and by some chemical transformations. Compounds 6 and 8 were characterized as their methyl ester derivatives (13 and 14, respectively). Most of the isolated compounds and some of their derivatives were tested as antimicrobial agents, but only 19 showed moderate inhibitory activity against Staphylococcus aureus.     

New luffariellolide derivatives from the Indonesian sponge Acanthodendrilla sp

Investigation of the Indonesian sponge Acanthodendrilla sp. afforded five new luffariellolide-related sesterterpenes, acantholides A-E (1-5), in addition to luffariellolide and its 25-O-methyl and 25-O-ethyl derivatives. All structures were unambiguously established by 1D and 2D NMR and MS spectroscopy. Acantholide D and E are derivatives comprising the 1-acetylcyclopentan-5-ol moiety, which are new variants of the C(14)-C(20) segment for this type of linear sesterterpenes. Luffariellolide and its 25-O-methyl congener as well as acantholide E (5) were cytotoxic against the mouse lymphoma L5187Y cell line. Acantholide B (2), luffariellolide, and its 25-O-methyl congener were active against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, the Gram-negative bacterium Escherichia coli, the yeast Candida albicans, and the plant pathogenic fungus Cladosporium herbarum.     

Oleanane saponins from Stylosanthes erecta

Five new oleanane saponins (1-5) together with four know flavonol glycosides were isolated from the aerial parts of Stylosanthes erecta. Their structures were elucidated by 1D and 2D NMR experiments including 1D-TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The aglycone moieties of 1-4 were assigned as new oleanane derivatives.     

Putrescine bisamides from Aglaia gigantea

Phytochemical analysis of the leaves of Aglaia gigantea collected in Vietnam yielded three cinnamoyl putrescine bisamide derivatives, which included the known compound dasyclamide ( 1), as well as two new natural products, gigantamide A ( 2) and grandiamide D ( 3). In this study, the structure of dasyclamide ( 1) was confirmed by X-ray crystallography. The structures of the two new alkaloids, gigantamide A ( 2) and grandiamide D ( 3), were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESIMS, HRQTOFMS) data. The absolute configuration of grandiamide D ( 3) was determined via Mosher ester derivatization.     

Ophiocerins A-D and ophioceric acid: tetrahydropyran derivatives and an africane sesquiterpenoid from the freshwater aquatic fungus Ophioceras venezuelense

Four new tetrahydropyran derivatives called ophiocerins A-D (1-4) and a new africane sesquiterpenoid (ophioceric acid; 5) have been isolated from cultures of the aquatic fungus Ophioceras venezuelense, together with the known compound regiolone. The structures and relative stereochemistry of these compounds were determined by analysis of 1D and 2D NMR data, while absolute stereochemical assignments for 1-4 were proposed by application of the exciton chirality CD method.     

Production of 8-demethylgeldanamycin and 4,5-epoxy-8-demethylgeldanamycin from a recombinant strain of Streptomyces hygroscopicus

Two new geldanamycin derivatives produced by genetic engineering of Streptomyces hygroscopicus strain K309-27-1 were isolated and characterized. Removal of the 8-methyl group of geldanamycin was achieved by replacing the AT4 domain of the polyketide synthase with a malonyl AT domain. The resulting strain produced 8-demethyl geldanamycin (2) and 4,5-epoxy-8-demethylgeldanamycin (3). The structures of both molecules were elucidated through interpretation of 1D and 2D NMR data as well as comparison with authentic geldanamycin derivatives. Compounds 2 and 3 displayed moderate cytotoxicity against the human breast cancer cell line SK-BR-3.     

New cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia membranacea

Bioassay-guided fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2-methylbutanoyloxy)cleroda-3,13(16),14-triene (7). The structures of 1-6 were established on the basis of extensive 1D and 2D NMR spectroscopic analysis. In addition, the new derivatives, 8 and 9, were prepared by acylation of 7 and 3, respectively. The isolated diterpenoids and their derivatives were tested against human prostate (PC-3) and hepatoma (Hep3B) cancer cells. Compounds 1, 3-5, and 7 exhibited cytotoxicity against both tumor cells, with IC(50) values below 3 micromicro, while compounds 2, 6, 8, and 9 were less effective.     

Triterpenes from Garcia parviflora. Cytotoxic evaluation of natural and semisynthetic friedelanes

Three new friedelane-type triterpenes, 1,2-dehydro-2,3-secofriedelan-3-oic acid (1), 1β-hydroxyfriedelin (2), and 3β-hydroxyfriedelan-23-oic acid (3), and the known compounds friedelin-3,4-lactone (4), acetyl aleuritolic acid (5), 4-hydroxy-5-propionyl-1,3-di-O-methylpyrogallol, elemicin, and (-)-syringaresinol were isolated from the leaves of Garcia parviflora. The structures of 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR, HREIMS, X-ray, and CD analysis. Some derivatives of 2 (6-14) were prepared via oxidation, reduction, and esterification. The natural triterpenes and the semisynthetic friedelane derivatives were tested for cytotoxic activity against human cancer cell lines U251, PC-3, K562, HCT-15, MCF-7, and SKLU-1. Compound 5 was cytotoxic against U251 cells.     

New diarylheptanoids and diarylheptanoid glucosides from the rhizomes of Tacca chantrieri and their cytotoxic activity

Two new diarylheptanoids (1, 2) and seven new diarylheptanoid glucosides (3-9) were isolated from the rhizomes of Tacca chantrieri. Their structures were determined by spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage. The absolute configurations of the 3,5-dihydroxyheptane moieties of the new diarylheptanoids were determined to be 3R and 5R by the application of the CD exciton chirality method to the corresponding 3,5-bis-p-bromobenzoyl derivatives. The cytotoxic activities of the isolated compounds and some derivatives against HL-60 human promyelocytic leukemia cells, HSC-2 human oral squamous carcinoma cells, and normal human gingival fibroblasts (HGF) are reported.     

New jaspamide derivatives from the marine sponge Jaspis splendans collected in Vanuatu

Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical structures were determined from 1D and 2D NMR studies and MS data. These two compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines with IC50 values in the microg/mL range.     

Antiplasmodial metabolites isolated from the marine octocoral Muricea austera

Bioassay-guided fractionation of the MeOH extract from the octocoral Muricea austera collected in the Pacific coast of Panama led to the isolation of eight compounds, including three tyramine derivatives (1-3), two steroidal pregnane glycosides (4, 5), and three sesquiterpenoids (6-8). Compounds 2-5 are new natural products, and their structures were determined on the basis of their spectroscopic data (HRMS, 1D and 2D NMR, and CD studies). The antiprotozoal activities of the natural compounds 1-8 as well as those of a series of synthetic glycosides (11-22) and tyramine derivatives (23-35) were evaluated in vitro against a drug-resistant Plasmodium falciparum and intracellular form of Trypanosoma cruzi.     

Cytotoxic isomalabaricane triterpenes from the marine sponge Rhabdastrella globostellata

Fourteen isomalabaricane triterpenes were isolated from the marine sponge Rhabdastrella globostellata. In addition to the known compounds globostellatic acids A (1) and D (4) and stelliferin riboside (13), 11 of the compounds were new natural products, which included globostelletin (3), eight new globostellatic acid congeners, F to M (2, 5-11), and two new stelliferin ribosides (12 and 14). The isolated compounds were tested against three different cancer cell lines, L5178Y (mouse lymphoma), HeLa (human cervix carcinoma), and PC-12 (rat pheochromocytoma). The isomalabaricane derivatives were found to be selectively active toward the mouse lymphoma cell line L5178Y. The structures were determined by 1D and 2D NMR data and by comparison with spectroscopic data of known related compounds.     

Cytotoxic phloroglucinols from the leaves of Myrtus communis

Bioactivity-guided fractionation of a dichloromethane extract of the leaves of Myrtus communis led to the isolation of phloroglucinol derivatives. The structures of the new myrtucommulones J, K, and L (1-3) and the previously known myrtucommulone A (4) were elucidated on the basis of extensive 1D and 2D NMR experiments as well as high-resolutionmass spectrometry. Myrtucommulone J was obtained as a tautomeric pair (1/1a). The compounds were tested in vitro for their cytotoxic and antibacterial activities.     

Izumiphenazines A-C: isolation and structure elucidation of phenazine derivatives from Streptomyces sp. IFM 11204

Three new phenazine derivatives, named izumiphenazines A-C (1-3), and the known phenazine-1,6-dicarboxylic acid (4) were isolated from Streptomyces sp. IFM 11204. The structures of the isolated compounds were elucidated by means of spectroscopic methods including UV, IR, HRESIMS, and 1D and 2D NMR. Compounds 1-3 were evaluated for their activity in overcoming TRAIL (TNF-related apoptosis-inducing ligand) resistance in human gastric adenocarcinoma cells. Compounds 2 (30 μM) and 3 (20 μM) in combination with TRAIL showed synergistic activity in sensitizing TRAIL-resistant AGS cells.     

The antibacterial ent-eusynstyelamide B and eusynstyelamides D, E, and F from the Arctic bryozoan Tegella cf. spitzbergensis

The brominated tryptophan-derived ent-eusynstyelamide B (1) and three new derivatives, eusynstyelamides D, E, and F (2-4), were isolated from the Arctic bryozoan Tegella cf. spitzbergensis. The structures were elucidated by spectroscopic methods including 1D and 2D NMR and analysis of mass spectrometric data. The enantiomer of 1, eusynstyelamide B, has previously been isolated from the Australian ascidian Eusynstyela latericius. Antimicrobial activities are here reported for 1-4, with minimum inhibitory concentrations (MIC) as low as 6.25 μg/mL for 1 and 4 against Staphylococcus aureus. Eusynstyelamides 2 and 3 showed weak cytotoxic activity against the human melanoma A 2058 cell line.     

New antioxidant hydroquinone derivatives from the algicolous marine fungus Acremonium sp

A marine fungal isolate, identified as Acremonium sp., was mass cultivated and found to produce two novel hydroquinone derivatives, 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol (1) and 7-isopropenylbicyclo[4.2.0]octa-1,3,5-triene-2,5-diol-5-beta-D-glucopyranoside (2). Compound 1 and its glucoside 2 possess a most unusual ring system. The new natural products (3R,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)naphthalenone (3) and (3S,4S)-3,4-dihydroxy-7-methyl-3,4-dihydro-1(2H)-naphthalenone (4) were obtained as a 1:0.8 mixture. 2-(1-Methylethylidene)pentanedioic acid (5) was isolated for the first time as a natural product and its structure proven by X-ray analysis. In addition to these compounds an inseparable mixture of three new isomeric compounds, pentanedioic acid 2-(1-methylethylidene)-5-methyl ester (6), pentanedioic acid 2-(1-methylethylidene)-1-methyl ester (7), and pentanedioic acid 2-(1-methylethenyl)-5-methyl ester (8), was also obtained. Isolated together with the new compounds were three known hydroquinone derivatives, 9, 10, and 11. The structures of all compounds were determined by interpretation of their spectroscopic data (1D and 2D NMR, MS, UV, and IR). Each isolate was tested for its antioxidant properties, and compounds 1 and 9-11 were found to have significant activity.     

Constituents of the Cuban endemic species Calophyllum pinetorum

A new prenylated xanthone, pinetoxanthone (1), and two new pyranochromanones, pinetoric acid I (2) and pinetoric acid II (3), together with 10 known compounds, namely, the triterpenes friedelin and canophyllol, the xanthone macluraxanthone, the pyranochromanone derivatives calophyllic acid, isocalophyllic acid, calolongic acid, apetalic acid, and isoapetalic acid, and the flavonoids amentoflavone and apigenin, were isolated from the stem bark and leaves of Calophyllum pinetorum, an endemic species in Cuba. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR experiments as well as HRESIMS analysis.     

Chromomoric acid derivatives from Tectona philippinensis

The air-dried leaves of Tectona philippinensis, an endemic and endangered Philippine medicinal tree, afforded four new chromomoric acid derivatives ( 1, 2, 3a, and 3b). Their structures were elucidated by extensive 1D and 2D NMR spectroscopy. Antimicrobial testing was carried out on 1- 3 against a panel of bacteria and fungi.