Beyerene derivatives and other constituents from Petunia patagonica

Two new diterpenes of the beyerene type, ent-19-hydroxy-1 7-acetoxybeyer-15-ene and ent-beyer-15-en-17-oic acid, and two previously characterized kauranoids, ent-16β-hydroxy-17-acetoxykaurane and ent-16β,1 7-dihydroxy-kaurane, as well as two known flavonoids, luteolin-7,3′,4′-trimethyl ether and luteolin-7,3′-dimethyl ether, and a triterpenoid, oleanoic acid, were obtained from a chloroform extract of Petunia patagonica. The new structures were elucidated by spectral data and chemical transformations.     

Diterpenoids and a sesquiterpene lactone from viguiera ladibractate

Eight known diterpene acids, ent-12-oxokaur-9(11),16-dien-19-oic acid, ent-12β-hydroxykaur-9(11),16-dien-19-oic acid, ent-isokaur-15(16)-en-17,19-dioic acid, ent-15α,16-epoxy-17-hydroxykaura-19-oic acid, ent-kaura-17,19-dioic acid, ent-kaur-16-en-19-oic acid, grandifloric acid, angeloyloxygrandifloric acid, as well as a new sesquiterpene lactone, ladibranolide, were isolated from Viguiera ladibractate. The stereochemistry of the sesquiterpene lactone was established by NOE experiments.     

Eudesmanolides and diterpenes from Wedelia trilobata and an ent-kaurenic acid derivative from Aspilia parvifolia

The reinvestigation of the aerial parts of Wedelia trilobata afforded, in addition to known compounds, six new eudesmanolides, two ent-kaurenic acid derivatives as well as a degraded one. A corresponding hydroxy compound was present in Gnaphalium undulatum. From Aspilia parvifolia new ent-kaurenic acid epoxides were isolated. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly.     

Ent-kauranes and trachylobanes from Helianthus radula

The aerial parts of Helianthus radula afforded a variety of known ent-kauranoic acids as well as two new substances, 11-oxotrachyloban-19-oic a     

Ent-kauren-19-oic acid derivatives from the stem bark of Croton pseudopulchellus Pax

Two new ent-kauren-19-oic acid derivatives, ent-14S*-hydroxykaur-16-en-19-oic acid and ent-14S*,17-dihydroxykaur-15-en-19-oic acid together with eleven known compounds ent-kaur-16-en-19-oic acid, ent-kaur-16-en-19-al, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid, 8R,13R-epoxylabd-14-ene, eudesm-4(15)-ene-1β,6α-diol, (?)-7-epivaleran-4-one, germacra-4(15), 5E,10(14)-trien-9β-ol, acetyl aleuritolic acid, β-amyrin, and stigmasterol were isolated from the stem bark of Croton pseudopulchellus (Euphorbiaceae). Structures were determined using spectroscopic techniques. Ent-14S*-hydroxykaur-16-en-19-oic acid, ent-kaur-16-en-19-oic acid, ent-12β-hydroxykaur-16-en-19-oic acid, ent-12β-acetoxykaur-16-en-19-oic acid and 8R,13R-epoxylabd-14-ene were tested for their effects on Semliki Forest virus replication and for cytotoxicity against human liver tumour cells (Huh-7 strain) but were found to be inactive. Ent-kaur-16-en-19-oic acid, the major constituent, showed weak activity against the Plasmodium falciparum (CQS) D10 strain.     

Biotransformation of 7α-hydroxy- and 7-oxo-ent-atis-16-ene derivatives by the fungus Gibberella fujikuroi

The microbiological transformation of 7α,19-dihydroxy-ent-atis-16-ene by the fungus Gibberella fujikuroi gave 19-hydroxy-7-oxo-ent-atis-16-ene, 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene, 7α,11β,19-trihydroxy-ent-atis-16-ene and 7α,16β,19-trihydroxy-ent-atis-16-ene, while the incubation of 19-hydroxy-7-oxo-ent-atis-16-ene afforded 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene and 16β,17-dihydroxy-7-oxo-ent-atisan-19-al. The biotransformation of 7-oxo-ent-atis-16-en-19-oic acid gave 6β-hydroxy-7-oxo-ent-atis-16-en-19-oic acid, 6β,16β,17-trihydroxy-7-oxo-19-nor-ent-atis-4(18)-ene and 3β,7α-dihydroxy-6-oxo-ent-atis-16-en-19-oic acid.     

Kaurenolide biosynthesis in a cell-free system from Cucurbita maxima seeds

A new product obtained by incubation of [2-¹⁴C ]-mevalonic acid with a cell-free system from Cucurbita maxima endosperm was identified by GC-MS as ent-kaura-6,16-dien-19-oic acid. When this compound was reincubated with the microsomal fraction it was converted to 7β-hydroxykaurenolide and hence to 7β,12α-dihydroxykaurenolide. The dienoic acid was also obtained by incubation of ent-kaurene, ent1-kaurenol, ent-kaurenal and ent-kaurenoic acid, but not ent-7α-hydroxykaurenoic acid, with the microsomal fraction. Thus, in the C. maxima cell-free system, the kaurenolides are formed by a pathway which branches from the GA pathway at ent-kaurenoic acid and proceeds via the dienoic acid.     

4β,19-Epoxy-norkaurene and other diterpenes from Mikania banisteriae

The aerial parts of Mikania banisterae afforded four new diterpenes, ent-kaur-16-en-18-al, 18-acetoxy-ent-kaurene, 18-hydroxy-16α,17-epoxy-ent-kaurane and 4β-19-epoxy-18-nor-ent-kaurene.     

Ent-beyerene and ent-atisene diterpenes from viguiera insignis

The new diterpenes, ent-beyer-15-ene-12α,19-diol and ent-atis-13-en-3β,16α-diol, were isolated as minor constituents from the aerial part of Viguiera insignis. The structures were established by biomimetic transformation, spectroscopic means and comparison with closely related compounds.     

Gibberellin A43 and other terpenes in endosperm of Echinocystis macrocarpa

By GC-MS the following acidic constituents of the endosperm of Echinocystis macrocarpa were identified: abscisic acid and its trans,trans-isomer, 4′-dihydrophaseic acid, GA₄, GA₇, iso-GA₇, GA₂₄, GA₂₅, two isomers of GA₁₃, GA₄₃, ent-6α,7α,17-trihydroxy-16αH-kauran-19-oic acid and ent-6α,7α, 16β, 17-tetrahydroxykauran- 19-oic acid. The structures of the last three new natural products were confirmed by partial synthesis. ent-Kaurene was detected in the neutral fraction.     

The microbiological transformation of some trachylobane diterpenoids by Gibberella fujikuroi

The microbiological transformation of ent-trachylobane, ent-7α-hydroxytrachylobane and ent-19-hydroxytrachylobane into trachylobagibberellins A₇, A₉, A₁₃, A₂₅, A₄₀ and A₄₇ by Gibberella fujikuroi is described. Whereas 7β-hydroxy- and 7β,18-dihydroxytrachylobanolides were obtained from ent-trachylobane and ent-trachyloban- 19-ol, the presence of a 7β-hydroxyl group directed metabolism exclusively into the gibberellin pathway. An 18-hydroxyl group as in ent-7α,18-dihydroxytrachylobane inhibited oxidation at C-6 affording ent-7α,18,19-trihydroxytrachylobane as the major metabolite.     

Biologically active abietane and ent-kaurane diterpenoids and other constituents from Erythroxylum suberosum

Bioassay-guided fractionation of the ethanol extract from the branches of Erythroxylum suberosum, which was toxic to brine shrimp larvae, afforded five diterpenes bearing abietane and ent-kaurane-type skeletons from an active fraction. From these, four were new, 7-oxo-16-hydroxy-abiet-15(17)-en-19-al, 16-hydroxyabiet-15(17)-en-7-one, 7α,16-dihydroxy-abiet-15(17)-en-19-al and ent-12α-hydroxy-kaur-16-en-19-al, while methyl ent-7α,15β-dihydroxy-kaur-16-en-19-oate is reported for the first time as a natural product. This is also the first reported occurrence of abietane-type diterpenes in the genus Erythroxylum. The flavonoid ombuin-3-rutinoside was isolated from an inactive fraction, while rutin (quercetin-3-rutinoside) was obtained from the non-toxic ethanol extract of the leaves. The structures of the new and known compounds were established by analyses of 1D- and 2D-NMR and mass spectrometry data.     

Differential metabolism of diastereoisomeric diterpenes by Preussia minima,found as endophytic fungus in Cupressus lusitanica

The plant diastereoisomeric diterpenes ent-pimara-8(14)-15-dien-19-oic acid, obtained from Viguiera arenaria, and isopimara-8(14)-15-dien-18-oic acid, isolated from Cupressus lusitanica, were distinctly functionalized by the enzymes produced in whole cell cultures of the fungus Preussia minima, isolated from surface sterilized stems of C. lusitanica. The ent-pimaradienoic acid was transformed into the known 7β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid, and into the novel diterpenes 7-oxo-8 β-hydroxy-ent-pimara-8(14)-15-dien-19-oic and 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acids. Isopimara-8(14)-15-dien-18-oic acid was converted into novel diterpenes 11α-hydroxyisopimara-8(14)-15-dien-18-oic acid, 7β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, and 1β,11α-dihydroxyisopimara-8(14)-15-dien-18-oic acid, along with the known 7β-hydroxyisopimara-8(14)-15-dien-18-oic acid. All compounds were isolated and fully characterized by 1D and 2D NMR, especially ¹³C NMR. The diterpene bioproduct 7-oxo-9β-hydroxy-ent-pimara-8(14)-15-dien-19-oic acid is an isomer of sphaeropsidin C, a phytotoxin that affects cypress trees produced by Shaeropsis sapinea, one of the main phytopathogen of Cupressus. The differential metabolism of the diterpene isomers used as substrates for biotransformation was interpreted with the help of computational molecular docking calculations, considering as target enzymes those of cytochrome P450 group.     

Millerenolides,sesquiterpene lactones from Milleria quinqueflora

The aerial parts of Milleria quinqueflora afforded 17 new germacranolides (five melampolides and 12 millerenolides), two ent-pimarene and two ent-kaurene derivatives as well as two alicyclic diterpenes and a galactoside. The structures were elucidated by NMR spectroscopy. The chemotaxonomic situation is discussed.     

Ent-kaurene diterpenoids and lignan from Leontopodium leontopodioides and their inhibitory activities against cyclooxygenases-1 and 2

Two new ent-kaurene diterpenoids, 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate)-β-d-glucopyranoside (leontocin A, 1), 13α,15α-dihydroxy-18-carboxy-19-nor-ent-kaur-16-ene-2β-O-(2′-angelate-6′-acetyl)-β-d-glucopyranoside (leontocin B, 2), and one new lignan, 2,3-bis[(3,4-di-hydroxyphenyl)methylene]-monoethyl ester-butanedioic acid (leontolignan A, 3), together with three known phenolic acids (4-6) were isolated from the aerial parts of Leontopodium leontopodioides (Asteraceae). Their structures were elucidated by chemical and spectroscopic methods. All isolates were evaluated for their anti-inflammatory activities by measuring their inhibitory effects against cyclooxygenase-1 and 2 in vitro.     

Chemical composition of Xylopia nitida: Diterpenes and alkaloids

From the roots of Xylopia nitida, were obtained a new natural diterpene, the ent-kaur-16-en-18,19-diol and a new aporphine alkaloid, the 5,6,6a,7-tetrahydro-1-methoxy-(6aS)-4H-benzo[de][1,3]benzodioxolo [5,6-g]quinoline. Some known compounds were also isolated, ent-trachylobane, ent-trachyloban-18,19-diol, ent-trachyloban-18-oic acid, ent-trachyloban-19-oic acid, (−)-xylopine, 1-O-ethyl-β-D-glucopyranose and a mixture of β-sitosterol and stigmasterol. This is the first phytochemical study about X. nitida. In this paper chemotaxonomic significance of these compounds is discussed.     

Two new ent-kaurene diterpene glucosides from the roots of Mikania micrantha

Two new ent-kaurene diterpene glucosides, β-d-glucopyranosyl-15α-(3-hydroxyl-3-methylbutanoyloxy)-ent-16-kauren-19-oate (1) and β-d-glucopyranosyl-15α-hydroxy-ent-16-kauren-19-oate (2), were isolated from the roots of Mikania micrantha. Their structures were elucidated on the basis of spectroscopic evidence. Both compounds were evaluated for allelopathic effects on the seed germination and seedling growth of Arabidopsis thaliana. Compound 1 inhibited the seedling growth by 68.3% at the concentration of 0.5 mM.     

Biotransformation of ent-kaur-16-ene and ent-trachylobane 7β-acetoxy derivatives by the fungus Gibberella fujikuroi (Fusarium fujikuroi)

Candol A (7β-hydroxy-ent-kaur-16-ene) (6) is efficiently transformed by Gibberella fujikuroi into the gibberellin plant hormones. In this work, the biotransformation of its acetate by this fungus has led to the formation of 7β-acetoxy-ent-kaur-16-en-19-oic acid (3), whose corresponding alcohol is a short-lived intermediate in the biosynthesis of gibberellins and seco-ring ent-kaurenoids in this fungus. Further biotransformation of this compound led to the hydroxylation of the 3β-positions to give 7β-acetoxy-3β-hydroxy-ent-kaur-16-en-19-oic acid (14), followed by a 2β- or 18-hydroxylation of this metabolite. The incubation of epicandicandiol 7β-monoacetate (7β-acetoxy-18-hydroxy-ent-kaur-16-ene) (10) produces also the 19-hydroxylation to form the 18,19 diol (20), which is oxidized to give the corresponding C-18 or C-19 acids. These results indicated that the presence of a 7β-acetoxy group does not inhibit the fungal oxidation of C-19 in 7β-acetoxy-ent-kaur-16-ene, but avoids the ring B contraction that leads to the gibberellins and the 6β-hydroxylation necessary for the formation of seco-ring B ent-kaurenoids. The biotransformation of 7β-acetoxy-ent-trachylobane (trachinol acetate) (27) only led to the formation of 7β-acetoxy-18-hydroxy-ent-trachylobane (33).     

Terpenoids and a flavan-3-ol from viguiera quinqueradiata

The isolation is reported of the new natural products from Viguiera quinqueradiata, acetylleptocarpin and (2R,3S-4′-hydroxy-3′,5,7-tri-O-methyl-flavan-3-ol. The diterpenes 15α-angeloyloxy-ent-kaur-16-en-19-oic acid, 15α-tigloyloxy-ent-kaur-16-en-19-oic acid and the sesquiterpene lactones leptocarpin and budlein A were also found.     

ent-Kaurane diterpenes from the stem bark of Annona vepretorum (Annonaceae) and cytotoxic evaluation

This work describes a novel ent-kaurane diterpene, ent-3β-hydroxy-kaur-16-en-19-al along with five known ent-kaurane diterpenes, ent-3β,19-dihydroxy-kaur-16-eno, ent-3β-hydroxy-kaur-16-eno, ent-3β-acetoxy-kaur-16-eno, ent-3β-hydroxy-kaurenoic acid and kaurenoic acid, as well as caryophyllene oxide, humulene epoxide II, β-sitosterol, stigmasterol and campesterol from the stem bark of Annona vepretorum Mart. (Annonaceae). Cytotoxic activities towards tumor B16-F10, HepG2, K562 and HL60 and non-tumor PBMC cell lines were evaluated for ent-kaurane diterpenes. Among them, ent-3β-hydroxy-kaur-16-en-19-al was the most active compound with higher cytotoxic effect over K562 cell line (IC₅₀ of 2.49 μg/mL) and lower over B16-F10 cell line (IC₅₀ of 21.02 μg/mL).