A new abietane and two dimeric abietane diterpenes from the black heartwood of Cryptomeria japonica

Three new diterpenes, sugikurojins A-C (1-3) were isolated from the black heartwood of Cryptomeria japonica. The structure of sugikurojin A was deduced to be 19-hydroxy-6,7-dehydroferruginol on the basis of extensive NMR experiments. Sugikurojin B was a dimer of 6,7-dihydroxyferruginol and 6,7-dehydroferruginol with a 6-O-11' linkage. Sugikurojin C was a dimeric ferruginol with 6-O-7' and 7-O-6' linkages. Also obtained in this investigation were the known compounds formosaninol (4), 15 sesquiterpenes (5-19), 16 diterpenes (20-35), three phenylpropanoids (36-38), and a phenolic compound (39).     

Abietane diterpenoids from the barks of Cryptomeria japonica

From the bark of Cryptomeria japonica were isolated sugikurojins I (1) and J (2), and an abietane derivative (3) was obtained for the first time as a natural product. These structures were elucidated primarily through extensive NMR experiments. Sugikurojin I (1) has a unique skeleton incorporating an abietane diterpene and a 1,10-secocadinane sesquiterpene. Sugikurojin J (2) is a peroxyester of hydroxyabietane diterpene and isopimarane acid diterpene. Compound 3 was p-quinone acid, which occurred by cleavage between C-7 and C-8 of sugiol; it was deduced to [4'-isopropyl-1(S),3,3-trimethyl-3',6'-dioxo-bicyclohexyl-1',4'-dien-2(R)-yl]-acetic acid. Also obtained in this investigation were three known diterpenes (4-6).     

Highly-oxygenated isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia and their nitric oxide inhibitory activity

From the methanolic extract of Indonesian Orthosiphon stamineus, nine new highly-oxygenated isopimarane-type diterpenes [7-O-deacetylorthosiphol B (1), 6-hydroxyorthosiphol B (2), 3-O-deacetylorthosiphol I (3), 2-O-deacetylorthosiphol J (4), siphonols A-E (5-9)] have been isolated together with nine known diterpenes [orthosiphols H (10), K (11), M (12) and N (13); staminols A (14) and B (15); neoorthosiphols A (16) and B (17); norstaminol A (18)]. Their structures were determined based on the spectroscopic data. The isolated diterpenes inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Compounds 4-7, 9, 10, 14, and 17 showed inhibitory activities more potent (IC(50), 10.8-25.5 microM) than a positive control N(G)-monomethyl-L-arginine (L-NMMA; IC(50), 26.0 microM).     

Sesquiterpene esters from the fruits of Celastrus orbiculatus

Three new beta-dihydroagarofuran sesquiterpene esters, 6 alpha-acetoxy-9 beta-benzoyloxy-1 beta-cinnamoyloxy-8 beta-butanoyloxy-beta-dihydroagarofuran (1), 6 alpha-acetoxy-9 beta-benzoyloxy-1 beta-cinnamoyloxy-8 beta-(2-methylbutanoyloxy)-beta-dihydroagarofuran (2), and 6 alpha-acetoxy-1 beta,8 beta-dibenzoyloxy-9 beta-hydroxy-beta-dihydroagarofuran (6), together with three known compounds (3-5) were isolated from the fruits of Celastrus orbiculatus THUNB. Their structures were elucidated on the basis of spectroscopic methods. Compound 4 showed moderate activity in inhibiting LPS-induced nitric oxide production in murine macrophage RAW264.7 cells with an IC(50) value of 43.7 microM.     

Rearranged vibsane-type diterpenes from Viburnum awabuki and photochemical reaction of vibsanin B

Nine new diterpenes, neovibsanin D (1), 7-epi-neovibsanin D (2), 15-O-methylneovibsanin F (3), 14-epi-15-O-methylneovibsanin F (4), 15-O-methyl-18-oxoneovibsanin F (5), 2-O-methylneovibsanin H (6), 2-O-methylneovibsanin I (7), neovibsanin G (8), and 14-epi-neovibsanin G (9), were isolated from a methanol extract of the leaves of Viburnum awabuki. Their structures were elucidated to be uniquely rearranged vibsane-type diterpenes by spectroscopic analyses and comparison of NMR data with those of previously reported vibsane-type diterpenes. In addition, irradiation of vibsanin B (12) in methanol with a high-pressure Hg lump led to the direct formation of neovibsanins A (14) and B (15). These results gave a clue to understanding of the biogenetic interconversion of 11-membered vibsanins into neovibsanins.     

Novel diterpenes from the heartwood of Chamaecyparis obtusa var. formosana

Two novel diterpenes, obtusanal B (1) and obtusadione (2), along with obtusanal A (3), obtunone (4), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial, 8,12-dihydroxydielmentha-5,9-diene-7,11-dione and myrcene, isolated from the heartwood of Chamaecyparis obtusa var. formosana, were characterized by spectroscopic means, including 2D-NMR techniques. Compounds 1 and 2 are 7(6-->2)abeoabietane and 14(8-->9)abeoabietane type diterpenes, respectively. Their biosyntheses were proposed.     

Four new podocarpane-type trinorditerpenes from the bark of Taiwania cryptomerioides

Further studies on the bark of Taiwania cryptomerioides found four new podocarpane derivatives, 1beta,13-dihydroxy-8,11,13-podocarpatriene (1), 14,18-dihydroxy-13-methoxy-8,11,13-podocarpatriene (2), 1beta,14-dihydroxy-13-methoxy-8,11,13-podocarpatriene-2,7-dione (3), and 3beta,14-dihydroxy-13-methoxy-8,11,13-podocarpatrien-7-one (4), together with a known 1beta,13,14-trihydroxy-8,11,13-podocarpatrien-7-one (5). Those structures were elucidated principally from spectral evidence.     

New norditerpenoids with trypanocidal activity from Vitex trifolia

Trypanocidal constituents of the fruits of Vitex trifolia were investigated. Activity-guided isolation of the acetone extract resulted in the isolation of two new norditerpene aldehydes, 1 and 2, together with five known diterpenes: vitexifolin E (3), vitexifolin F (4), vitexilactone (5), 6-acetoxy-9-hydroxy-13(14)-labden-16,15-olide (6), and previtexilactone (7). In vitro minimum lethal concentrations of the isolated compounds against epimastigotes of Trypanosoma cruzi were 11 microM (1), 36 microM (2), 34 microM (3), 34 microM (4), 66 microM (5), 66 microM (6), and >265 microM (7).     

The new cassane-type diterpenes from Caesalpinia minax

Four new cassane-type diterpenes, Neocaesalpin S (1), Neocaesalpin T (2), Neocaesalpin U (3), and Neocaesalpin V (4) were isolated from Caesalpinia minax HANCE together with seven known compounds Neocaesalpin A (5), Neocaesalpin K (6), Neocaesalpin L (7), Neocaesalpin M (8), Neocaesalpin O (9), Neocaesalpin MP (10), and Magnicaesalpin (11). Their structures were elucidated on the basis of 1D- and 2D-NMR, MS, and circular dichroism (CD) analysis. Compounds 1-4 were tested against liver cancer (HepG-2) and breast cancer (MCF-7), and showed mild antiproliferative activity.     

Cytotoxic sterols from marine-derived fungus Pennicillium sp

A new sterol, ergosta-8(14), 22-diene-3,5,6,7-tetraol(3beta, 5alpha, 6beta, 7alpha, 22E) (1), together with four known sterols ergosta-8(9), 22-diene-3,5,6,7-tetraol (3beta, 5alpha, 6beta, 7alpha, 22E) (2), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,22-diene-3beta-ol (3), 5alpha,8alpha-epidioxy-24(S)-methylcholesta-6,9(11), 22-triene-3beta-ol (4), 3beta,5alpha,9alpha-trihydroxyergosta-7,22-diene-6-one (5) was isolated from marine fungus Pennicillium sp. Their structures were determined based on chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-FAB-MS). Compounds 1-5 were evaluated for cytotoxicity against human liver cancer cell (Hep G), and most of them exhibited potent activity. Compound 1 display the highest potency with IC50 values 10.4 microg mL-1.     

Compounds with antiproliferative activity on five human cancer cell lines from South Korean Carpesium triste

In the search for antiproliferative compounds against human cancer cells (A549, SK-OV-3, SK-MEL-2, XF498, HCT15), it was found that the chloroform extracts obtained from the whole plant of Carpesium rosulatum Miq. (Compositae) exhibited significant cytotoxic activity. Two sesquiterpene lactones, CT-1 (2alpha,5-epoxy-5,10-dihydroxy-6-angeloyloxy-9beta-isobutyloxy-germacran-8alpha, 12-olide), and CT-2 (2beta,5-epoxy-5,10-dihydroxy-6alpha,9beta-diangeloyloxy-germacran-8alpha,12-olide) were isolated from the whole plant. CT-2 showed the most potent cytotoxicity with an IC50 value of 7.88 microM against SK-MEL-2.     

Simiranes A and B: erythroxylanes diterpenes and other compounds from Simira eliezeriana (Rubiaceae)

The first phytochemical study of Simira eliezeriana Peixoto (Rubiaceae) allowed the isolation and structural determination of two new diterpenes named simirane A [(5R,6R,8R,9R,10S,11S,13S)-6β,11β-dihydroxy-2,4(18),15-erythroxylatrien-1-one] (1) and simirane B [(5S,8R,9R,10S,11S,13S)-11β-hydroxy-2,4(18),15-erythroxylatrien-1-one] (2), together with seven known compounds: sitosterol (3), stigmasterol (4), campesterol (5), coniferaldehyde (6), vanillin (7), pinoresinol (8) and harman (9) from the bark of the plant. The structures of the compounds were established on the basis of spectroscopic methods, including 1-D and 2-D NMR, HRESI-MS and CD analysis and comparisons with available literature data of known compounds.     

Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines

The cytotoxicity of 39 compounds, including eighteen flavonoids (flavanones, 1-10; flavones, 11-17; flavanol, 18), sixteen phenolic acid derivatives (aromatic acids, 19-24; aldehyde, 25; esters, 26-34) and five glycerides (35-39), isolated from Mexican propolis, were evaluated against a panel of six different cancer cell lines; murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma and human HT-1080 fibrosarcoma. A phenylpropanoid-substituted flavanol, (2R,3S)-8-[4-phenylprop-2-en-1-one]-4',7-dihydroxy-3',5-dimethoxyflavan-3-ol (18), showed the most potent cytotoxicity against A549 cells (IC50, 6.2 microM) and HT-1080 cells (IC50, 3.9 microM), stronger than those of the clinically used anticancer drug, 5-fluorouracil (IC50, 7.5 microM and 5.4 microM, respectively). Based on the observed results, the structure-activity relationships are discussed.     

Endodesmiadiol, a friedelane triterpenoid, and other antiplasmodial compounds from Endodesmia calophylloides

From the ethyl acetate extract of the stem bark of Endodesmia calophylloides (Guttiferae), a novel friedelane triterpenoid named endodesmiadiol (1), as well as the known compounds friedelin (2), canophyllol (3), canophyllal (4), cerin (5), morelloflavone (6), volkensiflavone (7), 8-deoxygartanin (8), 3 beta-acetoxyoleanolic acid (9) and 1,8-dihydroxy-3-isoprenyloxy-6-methylxanthone (10) have been isolated. The structures of these compounds were established by spectroscopic analysis, and the relative configuration of endodesmiadiol (1) was confirmed by X-ray diffraction. The antiplasmodial activity of the isolated compounds was evaluated against the W2 strain of Plasmodium falciparum which is resistant to chloroquine and other antimalarial drugs. All the compounds were found to be active with IC50 values ranging from 7.2 to 23.6 microM. The IC50 of endodesmiadiol was found to be 11.8 microM.     

Five new diterpenoids from the bark of Taiwania cryptomerioides

Five new diterpenoids, 11-hydroxyabieta-8,11,13-trien-7-one (1), 11,12,14-trihydroxyabieta-8,11,13-trien-7-one (2), 6beta,7alpha-diacetoxyroyleanone (3), 7beta-hydroxymanoyl oxide (4), and 9alpha-hydroxyisopimara-8(14),15-dien-7-one (5) were obtained from the bark of Taiwania cryptomerioides. The structures of the new compounds 1-5 were elucidated on the basis of spectral analysis and chemical evidence.     

13C NMR Spectra of some diterpenes of Premna latifolia Roxb

¹³C NMR data are presented for premnolal (13-formyl-11,14-dihydroxypodocarpa-8,11,13-triene), the tetraacetate of nellionol (6α,11,14,16-tetra-O-acetylabieta-8,11,13-trien-7-one), 11-ketosandaracopimar-15-en-8β-ol, sandaracopimar-15-en-1β, 8β-diol and its l-keto derivative, and sandaracopimaran-1β,8β,12β-triol, obtained from Premna latifolia Roxb.     

Four New Podocarpane‐Type Trinorditerpenes from Aleurites moluccana

Four new podocarpane‐type trinorditerpenenes, (5β,10α)‐12,13‐dihydroxypodocarpa‐8,11,13‐trien‐3‐one ( 1 ), (5β,10α)‐12‐hydroxy‐13‐methoxypodocarpa‐8,11,13‐trien‐3‐one ( 2 ), (5β,10α)‐13‐hydroxy‐12‐methoxypodocarpa‐8,11,13‐trien‐3‐one ( 3 ), and (3α,5β,10α)‐13‐methoxypodocarpa‐8,11,13‐triene‐3,12‐diol ( 4 ), together with four known diterpenes, 12‐hydroxy‐13‐methylpodocarpa‐8,11,13‐trien‐3‐one ( 5 ), spruceanol ( 6 ), ent‐3α‐hydroxypimara‐8(14),15‐dien‐12‐one ( 7 ), and ent‐3β,14α‐hydroxypimara‐7,9(11),15‐triene‐12‐one ( 8 ), were isolated from the twigs and leaves of Aleurites moluccana. Their structures were elucidated by means of comprehensive spectroscopic analyses, including NMR and MS. Except 8 , all compounds were evaluated for their cytotoxicity; compound 4 exhibited moderate inhibitory activity against Raji cells with an IC₅₀ value of 4.24 μg/ml.     

Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products

Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11beta-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11beta, 17alpha,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11beta, 17alpha, 21-trihydroxy-5alpha-pregnan-3, 20-dione (4) and 3beta, 11beta, 17alpha, 21-tetrahydroxy-5alpha-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 microM) and 4 (IC50 157 microM) have shown significant inhibitory activity against PEP.