Effect of some ent-kaurenes on the viability of human peripheral blood mononuclear cells

The possible cytotoxic activity of some ent-kaurenes on human mononuclear cells, obtained from peripheral blood, was studied having in mind future studies on their antitumor activity. The cells were obtained using the Ficoll-Hypaque method, adjusted to 2 x 10(6) cells/mL, and incubated with kaurenes for 48 hours at 3 x 10(-5), 30 x 10(-5), 300 x 10(-1) and 3000 x 10(-5) micromol/well. Ent-kaurenic acid showed no toxicity at all concentrations studied. The least toxic of all the kaurene derivatives studied was ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid, with a cellular viability of 99% at 3 x l0(-5) micromol/well, and 94% at 30 x 10(-1) micromol/well. Another compound that showed low toxicity was the 2,3,4,6-tetra-acetyl-alpha-D-pyranosyl ester of ent-15-oxo-(-)-kaur-16-en-19-oic acid with 44% viability at 3000 x 10(-5) micromol/well. The most toxic compounds at all concentrations tested were ent-kaur-16-en-19-ol acetate and ent-16alpha-hydroxy-(-)-kauran-19-oic acid. On the other hand, ent-kaur-9(11)16-dien-19-oic acid, ent-kauran-19-oic acid, and ent-kaur-16-en-19-ol were toxic only at the highest concentration studied. According to these results, and considering the concentrations employed, ent-kaur-16-en-19-oic acid and ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid could be used for in vivo experiments and possibly for therapeutic purposes on humans, without much risk.     

ent-pimarane-type diterpenoids from Siegesbeckia orientalis L

A new ent-pimarane glucoside, named hythiemoside B (4), was isolated from the aerial part of Siegesbecikia orientalis L. (Asteraceae) together with four known ent-pimarane-type diterpenoids: darutigenol (1), darutoside (2), hythiemoside A (3), and ent-(15R),16,19-trihydroxypimar-8(14)-ene 19-O-beta-D-glucopyranoside (5). The structure of the new compound was elucidated by spectroscopic analyses and chemical transformation. The NMR data of compounds 1 (1H-) and 5 (1H- and 13C-) were also compiled in this study on the basis of 2D experiments.     

Licamichauxiioic-A and -B acids--two ent-kaurene diterpenoids from Licania michauxii

Bioassay-guided fractionation allowed the isolation of two new cytotoxic ent-kaurene diterpenoids, licamichauxiioic-A and -B acids (1 and 2) from the root extract of Licania michauxii Prance (Chrysobalanaceae). They were characterized as ent-15-oxo-9(11),16-kauradien-19-oic acid (1) and ent-15-oxo-13(14),16-kauradien-19-oic acid (2) by various spectroscopic methods, in particular, 1D and 2D NMR spectra, and chemical evidence.     

Cytotoxic diterpenoids from Vietnamese medicinal plant Croton tonkinensis GAGNEP

Six new ent-kaurane-type diterpenoids were isolated from the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae) together with three known ent-11alpha-acetoxy-7beta,14alpha-dihydroxykaur-16-en-15-one (1), ent-kaur-16-en-15-one 18-oic acid (5) and ent-18-hydroxykaur-16-ene (7). Their structures were determined by spectroscopic analyses to be ent-7beta-acetoxy-11alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-11alpha-hydroxykaur-16-en-15-one (3), ent-11alpha-acetoxykaur-16-en-18-oic acid (4), ent-15alpha,18-dihydroxykaur-16-ene (6), ent-11alpha,18-diacetoxy-7beta-hydroxykaur-16-en-15-one (8), and ent-(16S)-1alpha,14alpha-diacetoxy-7beta-hydroxy-17-methoxykauran-15-one (14). ent-Kaurane-type diterpenoids from Croton tonkinensis 2-4, 6, and 9-13, were tested for toxicity in the brine shrimp lethality assay. Compounds 9, 10, and 12 demonstrated significant activity, compounds 2, 3, 6, and 11 showed weak activity, and compounds 4 and 13 were inactive.     

Terpenoids from Turraeanthus species

Chemical investigation of the root bark of Turraeanthus mannii and the stem of T. longipes resulted in the isolation of two new diterpenes, 13-methyl-labda-8(17)-en-15-oic acid (1) and 13-(hydroxymethyl)-14-hydroxy-ent-labda-8(17)-en-15-oic acid (2), along with two known diterpenes, 19-hydroxy-ent-labda-8(17),13-dien-15,16-olide (3) and 19-acetoxy-ent-labda-8(17),13-dien-15,16-olide (4), and the phytosterol, stigmasterol. The structure elucidation of the new compounds has been achieved using spectroscopic techniques.     

Four ent-kaurane-type diterpenoids from Croton tonkinensis Gagnep

From the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae) the four new ent-kaurane-type diterpenoids ent-1alpha,14alpha-diacetoxy-7beta-hydroxykaur-16-en-15-one (1), ent-1alpha,7beta-diacetoxy-14alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-14alpha-hydroxykaur-16-en-15-one (3), and ent-(16S)-18-acetoxy-7beta-hydroxykauran-15-one (4) were isolated. Their structures were elucidated by spectroscopic analyses.     

Terpenoids from Chloranthus multistachys

Two new diterpenoids, ent-17-hydroxyl-16beta-methoxyl-kauran-3-one (1) and ent-17-acetoxyl-16beta-methoxyl-kauran-3-one (2), along with nine known compounds (3-12), ent-17-hydroxyl-kaur-15-en-3-one (3), ent-3beta-acetoxyl-kaur-15-en-16beta, 17-diol (4), ent-kauran-3beta, 16beta, 17-triol (5), ent-3beta-acetoxyl-kauran-16beta, 17-diol (6), ent-kauran-16beta, 17-diol (7), abbeokutone (8), ent-17alpha-acetyl-16beta-hydroxyl- kauran-3-one (9), shizukaol F (10), cycloshizukaol A (11) and curcolonol (12), were isolated from Chloranthus multistachys (Chloranthaceae). Their structures were elucidated by spectroscopic spectra.     

Three diterpenoids (excoecarins V1-V3) and a flavanone glycoside from the fresh stem of Excoecaria agallocha

Three new diterpenoids, excoecarins V1-V3 (1-3) and a new flavanone glycoside (7) were isolated from the fresh stem of Excoecaria agallocha L. Their structures were elucidated as: 2alpha,3alpha,18-trihydroxy-3beta,20-epoxybeyer-15-ene (1), ent-2,3-secokaur-16-en-2,3-dioic acid (2), ent-3,4-seco-16alpha-hydroxyatis-4(19)-en-3-oic acid (3), and 3,5,7,3',5'-pentahydroxy-2R,3R-flavanonol 3-O-alpha-L-rhamnopyranoside (7) on the basis of spectroscopic data, chemical evidence, and/or X-ray analysis.     

Diterpenes from Sideritis trojana

Six known ent-kaurene, a new ent-kaurane and a new pimarane diterpenes were isolated from Sideritis trojana. The structures of new compounds were determined as ent-7alpha-15beta,16beta-epoxykaurane (1), and ent-2alpha-hydroxy-8(14),15-pimaradiene (2) along with the known compounds siderol (3), sideridiol (4), 7-epicandicandiol (5), isocandol B (6), candol A acetate (7) ent-7alpha-acetoxykaur-15-ene (8) by IR, 1D and 2D NMR techniques and HRMS.     

Two new ent-kaurane diterpenoids from the aerial parts of Isodon excisoides简

Two new ent-kaurane diterpenoids, ent-7a,14b-dihydroxykaur-16-en-15-one-20-oic acid(1) and 1,7a,12b,14b-tetrahydroxy-1,10-seco-ent-kaur-10,16-dien-15-one(2), together with six known ones(3–8), were isolated from the EtOAc extract of the aerial parts of Isodon excisoides. Their structures were elucidated on the basis of 1D NMR and 2D NMR analyses as well as HR-ESI-MS experiments.     

Labdane diterpenes from the rhizomes of Hedychium coronarium

A new labdane diterpenoid, (E)-labda-8(17),12-dien-15,16-olide (1) together with eight known compounds, coronarin D (2), coronarin D methyl ether (3), coronarin D ethyl ether (4), isocoronarin D (5), coronarin B (6), labda-8(17),11,13-trien-15,16-olide (7), (E)-labda-8(17),12-diene-15,16-dial (8) and 16-hydroxylabda-8(17),11,13-trien-15,16-olide (9), are isolated from the rhizomes of Hedychium coronarium. Compounds 2-4, 5 and 9 are isolated as mixtures of C-15, C-14 and C-16 epimers, respectively. Their structures are determined on the basis of their spectroscopic data. The epimeric mixtures of 2 and 3 have not been reported before. Some of them were evaluated for their cytotoxicity.     

Terpenoids and phenolics from Plectranthus strigosus, bioactivity screening

Further studies on Plectranthus sp. (Lamiaceae) led to the isolation of terpenes and phenol esters from Plectranthus strigosus Benth. ent-16-Kauren-19-ol (1), ent-16-kauren-19-oic acid (2), xylopic acid (3), xylopinic acid (4), hinokiol (5), 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-9-ene (6) 4 beta,6 beta-dihydroxy-1 alpha,5 beta(H)-guai-10(14)-ene (7), mixtures of hexacosan-1,26-diol and octacosan-1,28-diol ferulate diesters (8), of esters from ferulic acid and fatty alcohols (9) and of esters from fatty acids and 2-(4-hydroxyphenyl)-ethanol (10) were for the first time isolated from this genus. Supplementary spectral data for 3,8 and parvifloron D (11) metabolites are also presented. A bioactivity study revealed herpetic inhibitory properties for (1) and (2), and antioxidant ability for (5) and (8) phenolic constituents.     

A new synthesis of a potent cancer chemopreventive agent, 13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid from trans-communic acid

The first synthesis of a labdane diterpenoid, (-)-13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid [(-)-1a], isolated from the stem bark of Thuja standishii (GORD.) CARR., from the major component trans-communic acid (3a) is described.     

Metabolism of 32-oxo-24,25-dihydrolanosterols by partially purified cytochrome P-450(14DM) from rat liver microsomes

Metabolism of 32-oxo-24,25-dihydrolanosterols (3 beta-hydroxylanost-8-en-32- al (4,delta 8-CHO) and 3 beta-hydroxylanost-7-en-32-al (5,delta 7-CHO)) was studied in a reconstituted system consisting of rat liver partially purified cytochrome P-450, which catalyzes lanosterol 14-demethylation (P-450(14DM)), and reduced nicotineamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase. The reconstituted system converted delta 8-CHO to 4,4-dimethyl-5 alpha-cholesta-8,14-dien-3 beta-ol (2, 8, 14-Diene), which corresponds to the 14-deformylated product. delta 7-CHO, the isomer of delta 8-CHO, was not converted to the corresponding 14-deformylated product. The apparent Km value of cytochrome P-450(14DM) for delta 8-CHO was about 1/20 of that for 24,25-dihydrolanosterol (1, DHL). The metabolism of delta 8-CHO was inhibited by 7-oxo-24,25-dihydrolanosterol (6, 7-oxo-DHL), which is a potent inhibitor of cholesterol biosynthesis from lanosterol or DHL. However, the metabolism of delta 8-CHO was less inhibited by 7-oxo-DHL than that of DHL.     

A new labdane-type diterpene from the bark of Juniperus chinensis Linn

From the bark of Juniperus chinensis Linn., a new labdane-type diterpene, methyl 14,15-dihydroxy-8(17),12E-labdadien-19-oate (1a), together with nine known compounds, trans-communic acid, cis-communic acid, 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid, sandaracopimaric acid, 7-oxosandaracopimaric acid, sugiol, 7-oxototarol, alpha-cedrol and beta-sitosteryl-1-O-beta-glucopyranoside were isolated. The structures of those compounds were elucidated based on spectral analysis and chemical evidences.     

New lanostane-type triterpenes from Fomes officinalis

Five new lanostane-type triterpenes, named fomefficinic acid A-E (1-5), were isolated from the dried sclerotium of Fomes officinalis, respectively. Their structures were established as 24-methylene-3-oxo-lanost-8-en-21-oic acid (1), 3alpha,15alpha-dihydroxy-24-methylene-lanosta-7,9(11)-dien-21-oic acid (2), 3alpha,15alpha-dihydroxy-24-methylene-lanost-8-en-21-oic acid (3), 15alpha-hydroxy-3-oxo-24-methylenelanost-8-en-21-oic acid (4), 15alpha-acetoxy-3-oxo-24-methylenelanosta-7,9(11)-dien-21-oic acid (5), by spectral analysis and chemical methods as well as comparison with known compounds.     

Anticariogenic properties of ent-pimarane diterpenes obtained by microbial transformation

In the present work, the anticariogenic activities of three pimarane-type diterpenes obtained by fungal biotransformation were investigated. Among these metabolites, ent-8(14),15-pimaradien-19-ol was the most active compound, displaying very promising MIC values (ranging from 1.5 to 4.0 μg mL(-1)) against the main microorganisms responsible for dental caries: Streptococcus salivarius, S. sobrinus, S. mutans, S. mitis, S. sanguinis, and Lactobacillus casei. Time kill assays performed with ent-8(14),15-pimaradien-19-ol against the primary causative agent S. mutans revealed that this compound only avoids growth of the inoculum in the first 12 h (bacteriostatic effect). However, its bactericidal effect is clearly noted thereafter (between 12 and 24 h). The curve profile obtained by combining ent-8(14),15-pimaradien-19-ol and chlorhexidine revealed a significant reduction in the time necessary for killing S. mutans compared with each of these two chemicals alone. However, no synergistic effect was observed using the same combination in the checkerboard assays against this microorganism. In conclusion, our results point out that ent-8(14),15-pimaradien-19-ol is an important metabolite in the search for new effective anticariogenic agents.     

Reaction of methyl 1-bromocycloalkanecarboxylates with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates

Methyl 1-bromoalkanecarboxylates react with zinc and ethyl 5-aryl-3-oxo-2,2-diethylpent-4-enoates to form ethyl 2-(10-aryl-6-oxo-7-oxaspiro[4.5]dec-8-en-8-yl)-2-ethylbutanoates and ethyl 2-(5-aryl-1-oxo-2-oxaspiro[5.5]undec-3-en-3-yl)-2-ethylbutanoates.     

Asymmetric synthesis of methyl (-)-13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oate, methyl ester of a potent suppressor toward carcinogenic promotor

Asymmetric synthesis of methyl ester (4) of (-)-13-oxo-15,16-dinorlabda-8(17),11E-dien-19-oic acid (1), which exhibited the most potent activity for the prevention of incipient carcinogenesis among the isolated diterpenes from Thuja standishii and its related plants, was achieved by using methyl (-)-1,4a-dimethyl-5-oxodecahydronaphthalene-1-carboxylate (5) as a strating material, which was easily prepared on gram scale by baker's yeast-catalyzed asymmetric reduction.     

Clerodane diterpenoids from Microglossa angolensis

Two new diterpenoids, 6β-(2-methylbut-2(Z)-enoyl)-3α,4α,15,16-bis-epoxy-8β,10βH-ent-cleroda-13(16),14-dien-20,12-olide and 10β-hydroxy-6-oxo-3α,4α,15,16-bis-epoxy-8βH-cleroda-13(16),14-dien-20,12-olide, together with the known β-amyrin, spinasterol, 5,7-dihydroxy-3,8,3′,4′-tetramethoxyflavone and 5,7-dihydroxy-3,8,3′,4′,5′-pentamethoxyflavone have been isolated from the aerial parts of Microglossa angolensis Oliv. et Hiern (Compositae). The structures were elucidated on the basis of spectral studies and comparison with published data.