Cytotoxic clerodane diterpenoids from fruits of Casearia grewiifolia

Bioactivity-guided fractionation of the ethyl acetate-soluble fraction of a methanol extract of the fruits of Casearia grewiifolia afforded eight new clerodane diterpenes, caseargrewiins E-L (1-8), and a known clerodane diterpene, esculentin B (9). The structures of 1-8 were established on the basis of 1D and 2D NMR spectroscopic data. Most of these compounds exhibited cytotoxicity against three cancer cell lines with IC50 values in the range 0.15-6.00 microg/mL.     

Novel bioactive clerodane diterpenoids from the leaves and twigs of Casearia sylvestris

Fractionation of a methanol extract of the leaves and twigs of Casearia sylvestris, as directed by activity against KB cell cytotoxicity, led to the isolation of three novel clerodane diterpenoids, casearvestrins A-C (1-3). The structures of 1-3 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on ROESY correlations and COSY coupling constants. All three compounds displayed promising bioactivity, both in cytotoxicity assays against a panel of tumor cell lines and in antifungal assays via the growth inhibition of Aspergillus niger in a disk diffusion assay.     

Cytotoxic clerodane diterpenoids from Casearia membranacea

Bioassay-guided fractionation of the EtOAc extract of Casearia membranacea leaves and twigs afforded three new clerodane diterpenes, caseamembrins M-O (1-3), and the known rel-(2S,5R,6R,8S,9S,10R,18S,19R)-2-(2-methylbutyryloxy)-6-hydroxy-18,19-di-O-acetyl-18,19-epoxycleroda-3,13(16),14-triene (4) and caseamembrin D (5). The structures of 1-3, including the relative configurations, were established by extensive NMR spectroscopic analyses. The cytotoxic activities of the isolated diterpenoids against human oral epidermoid (KB), medulla (Med), and colon (DLD-1) cancer cell lines were evaluated.     

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.     

Structure and stereochemistry of new cytotoxic clerodane diterpenoids from the bark of Casearia lucida from the Madagascar rainforest

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the bark of Casearia lucida resulted in the isolation of 11 new clerodane diterpenes, namely, casearlucins A-K (1-11), and three known clerodane diterpenoids, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-hydroxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (12), rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-6-methoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (13), and rel-(2S,5R,8S,9S,10R,18S,19R)-18,19-diacetoxy-18,19-epoxy-2-(2xi-methylbutanoyloxy)cleroda-3,13(16),14-triene (14). The structures of compounds 1-11 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All compounds exhibited cytotoxicity activity against the A2780 ovarian cancer cell line, but none of the six compounds selected for testing in multiple cell lines showed significant selectivity.     

Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar

Bioassay-guided fractionation of the cytotoxic leaf and flower extract of Casearia nigrescens led to the isolation of four new clerodane diterpenoids, designated caseanigrescens A-D (1-4). These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3. The structures of compounds 1-4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83-1.4 microM.     

Cytotoxic clerodane diterpenes from Casearia rupestris

Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6). All compounds were evaluated for cytotoxicity against a small panel of human cancer cell lines. Casearupestrin A (1) exhibited the most potent activity against MDA/MB-435 (human melanoma) and SF-295 (human glioblastoma) cells, superior to that of the standard drug doxorubicin.     

Four new clerodane diterpenoids from Callicarpa pentandra

Leaf extracts of Callicarpa pentandra provided four new clerodane-type diterpenoids (1-4), of which 1, 2, and 4 have ring-A-contracted structures. Their structures and stereochemistry were established by spectral data interpretation, and for 3 also by single-crystal X-ray diffraction.     

Echinophyllins C-F, new nitrogen-containing clerodane diterpenoids from Echinodorus macrophyllus

Four new nitrogen-containing clerodane diterpenoids, echinophyllins C-F (1-4), were isolated from the leaves of the Brazilian medicinal plant Echinodorus macrophyllus ("Chapéu-de-couro"), and their structures and relative stereochemistry were elucidated from their spectroscopic data. Compounds 1-4 possess an alpha,beta-unsaturated gamma-lactam ring consisting of a clerodane diterpene unit and an amine moiety.     

Abietane diterpenoids from the bark of Cryptomeria fortunei

Four new abietane diterpenoids, fortunins A-D (1-4), and six new 18-hydroxymethylene abietane diterpenoids, fortunins E-J (5-10), along with 12 known diterpenoids, were isolated from the bark of Cryptomeria fortunei. The structures of new compounds were established on the basis of 1D and 2D NMR and other spectroscopic analyses.     

Taxane diterpenoids from the stem bark of Taxus mairei

Three new 11(15-->1)-abeo-taxanes, taxumairols U-W (1-3), have been isolated from extracts of the stem bark of Formosan Taxus mairei. The structures of 1-3 were identified as 5alpha,7beta,9alpha,13alpha,20-pentaacetoxy-2alpha,10beta,15-trihydroxy-11(15-->1)-abeo-taxene, 5alpha,7beta,9alpha,20-tetraacetoxy-2alpha,10beta,13alpha,15-tetrahydroxy-11(15-->1)-abeo-taxene, and 2alpha,4alpha,7beta,10beta-tetraacetoxy-5beta,20-epoxy-9alpha,13alpha,15-trihydroxy-11(15-->1)-abeo-taxene, respectively, on the basis of 2D NMR techniques including COSY, HSQC, HMBC, and NOESY experiments as well as chemical reactions of compounds 1-3 to give 4 (5alpha,7beta,9alpha,10beta,13alpha,20-hexaacetoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene) and 5 (4alpha,7beta,10beta-triacetoxy-9alpha,13alpha-dibenzoxy-5beta,20-epoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene), which are also novel taxane derivatives. Taxumairols U (1) and V (2) exhibited significant cytotoxicities against human hepatoma tumor cells, while taxumairol W (3) was inactive.     

Tigliane diterpenoids from the stem bark of Neoboutonia macrocalyx

Neoboutonia macrocalyx is a plant used by traditional healers among the Meru community in Kenya. Chromatographic fractionation of the petroleum ether and dichloromethane extracts of this plant yielded one known (1) and three new tigliane-type diterpenoids (2-4). The chemical structures of the isolated compounds were established through spectroscopic data interpretation.     

Porwenins A and B, new clerodane diterpenoids from Portulaca okinawensis.

Two new clerodane-type diterpenes, porwenins A (1) and B (2), were isolated from Portulaca okinawensis, and the structures were elucidated by spectroscopic data.     

Potential antitumor-promoting diterpenoids from the stem bark of Picea glehni

A novel rearranged labdane-type diterpenoid, 19(4-->3)abeo-8alpha, 13(S)-epoxylabda-4(18),14-diene (1), and two new abietane-type diterpenoids, 19-nor-abieta-4(18),8,11,13-tetraen-7-one (2) and 12-hydroxydehydroabietic acid (3) were isolated from the stem bark of Picea glehni, together with seven known diterpenoids-13-epimanoyl oxide (4), dehydroabietic acid (5), (11E)-14, 15-bisnor-8alpha-hydroxy-11-labden-13-one (6), abieta-8,11, 13-trien-7-one (7), 9alpha,13alpha-epidioxyabiet-8(14)-en-18-oic acid (8), 9,10alpha-epoxy-9,10-seco-abieta-8,11,13-trien-18-oic acid (9), and methyl 15-hydroxy-7-oxo-dehydroabietate (10). Compounds 5-8 and 10 showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate.     

Cytotoxic diterpenoids from the bark of Pseudolarix kaempferi and their structure-activity relationships

Four new diterpenoids, 11S-deacetylpseudolaric acid A (2), deacetylpseudolaric acid A O-beta-d-glucopyranoside (3), deacetylpseudolaric acid A 2,3-dihydroxypropyl ester (4), and deacetylpseudolaric acid B 2,3-dihydroxypropyl ester (5), and nine known diterpenoids were isolated from the bark of Pseudolarix kaempferi. Their structures were determined on the basis of chemical and spectroscopic analyses. In addition, their in vitro cytotoxic activities against three human cancer cell lines and their structure-activity relationships were evaluated.     

New diterpenoids from Viburnum awabuki

Eight new vibsane-type diterpenoids, vibsanins P-W (1-8), were isolated from the methanol extracts of the leaves and twigs of Viburnum awabuki. The structures were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

Klymollins A-H, bioactive eunicellin-based diterpenoids from the formosan soft coral Klyxum molle

Eight new eunicellin-based diterpenoids, klymollins A-H (1-8), were isolated during the chemical investigation of the soft coral Klyxum molle from Taiwan waters. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 4 was determined by Mosher's method. Bioassays of the new metabolites showed that compounds 3-8 displayed significant in vitro anti-inflammatory activity by inhibiting the expression of the iNOS protein, and compounds 3, 4, and 6-8 also could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.     

New bis-secolabdane diterpenoids from Excoecaria agallocha

Two new bis-secolabdane diterpenoids, excoecarins R1 (1) and R2 (2), were isolated from the resinous wood of Excoecaria agallocha. The structures of 1 and 2 were established on the basis of spectroscopic data interpretation and chemical evidence.     

New diterpenoids from the marine mangrove Bruguiera gymnorrhiza

Phytochemical investigation of the stem of Bruguiera gymnorrhiza yielded three new ent-kaurane diterpenoids (1, 2, and 3) and one new ent-beyerane diterpenoid (4) together with nine known ent-kaurane diterpenoids. All structures and the relative stereochemistry of the new compounds were determined by NMR spectroscopic studies. The absolute stereochemistry of 4 was determined by CD data. Some of the compounds showed moderate cytotoxic properties.