Resin acids of Pinus resinosa needles

The principal resin acids in the needles of Pinus resinosa are the labdane diterpenes, the new 8,13-epoxy-14-labden-19-oic acid (epimanoyl oxide acid), 8,13β-epoxy-14-labden-19-oic acid (manoyl oxide acid), 8(17),E-12,14-labdatrien-19-oic acid (communic acid) and 15-oxo-8(17)-labden-19-oic acid (imbricataloic acid). A survey of needles from representative populations of P. resinosa showed a limited variability in resin acid composition consistent with the uniformity of other traits. The composition of needle resin acids for putative P. nigra x resinosa hybrids strongly suggests the improbability of P. resinosa as the pollen parent.     

Sesquiterpene lactone and diterpene constituents of helianthus annuus

One new furanoheliangolide derivative, 4,5-dihydroniveusin A, as well as the known compounds niveusin B and argophyllin A and B, were isolated from a Texas population of Helianthus annuus. Three previously characterized diterpene acids, grandifloric acid, ciliaric acid and 17-hydroxy-ent-isokaur-15(16)-en-19-oic acid were the principal constituents of this population.     

Bioconversion of Lithocholic Acid Under Anaerobic Conditions by Pseudomonas sp. Strain NCIB 10590

The biotransformation of lithocholic acid by Pseudomonas sp. strain NCIB 10590 under anaerobic conditions was studied. The major products were identified as androsta-1,4-diene-3,17-dione and 3-oxochol-4-ene-24-oic acid. The minor products included 17β-hydroxyandrost-4-ene-3-one, 17β-hydroxyandrosta-1,4-diene-3-one, 3-oxo-5β-cholan-24-oic acid, 3-oxochola-1,4-diene-24-oic acid, 3-oxopregn-4-ene-20-carboxylic acid, and 3-oxopregna-1,4-diene-20-carboxylic acid. Anaerobiosis increases the number of metabolites produced by Pseudomonas sp. NCIB 10590 from lithocholic acid.     

Secobeyerene diterpenes from Beyeria calycina

Two new secobeyerene acids have been isolated from Beyeria calycina var. minor and their structures identified as ent-6α,17-dihydroxy-3,4-secobeyer-15-en-3-oic acid and (4S)-ent-18-hydroxy-3,4-secobeyer-15-ene-3,17-dioic acid. Distinct pathways are involved in the formation of the former compound and the major seco acid component.     

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.     

Resin acids from two amazonian species of Hymenaea

The major diterpene acid constituents of two Amazonian species of Hymenaea have been isolated and identified. A new resin acid, guamáic acid, is described.     

Rare,seven-membered cyclic ether labdane diterpenoid from Dodonaea polyandra

Previous phytochemical studies on the leaf resin of dioecious plant species Dodonaea polyandra have identified the presence of furanoclerodane diterpenoids. As part of ongoing research on this species the chemical profile of an individual plant displaying male flowers was investigated. Repeated chromatographic separation of a resinous extract from the leaves of the plant yielded three labdane diterpenoids, 13,17-epoxy-13-methyl-15-oxo-labda-7-ene (1), 17-hydroxy-13-methyl-labda-7,13Z-diene-15-oic acid (2) and 13-methyl-17-oxo-labda-7,13Z-diene-15-oic acid (3) and a fourth known labdane diterpenoid (4) reported as being isolated from a natural source for the first time. Structural elucidation was carried out using conventional 1D and 2D NMR and mass spectrometry together with other complementary techniques (UV and IR). The leaf extract from this individual of D. polyandra with male flowers present displays a marked difference in the chemical composition of diterpenoids compared to previously studied extracts from the leaves of this species.     

Apocarotenoids from Cochlospermum tinctorium

Seven carotenoids have been isolated from Cochlospermum tinctorium by means of countercurrent chromatography and HPLC. The two major constituents were identified by spectroscopic methods (UV-VIS, IR, ¹H NMR, ¹³C NMR and EIMS) as 6-hydroxy-8′-apo-ε-caroten-3-one-8′-oic acid (cochloxanthin) and 4,5-dihydro-6-hydroxy-8′-apo-ε-caroten-     

The biotransformation of hyodeoxycholic acid by Pseudomonas sp. NCIB 10590 under anaerobic conditions

The bacterial degradation of hyodeoxycholic acid under anaerobic conditions was studied. The major acidic product has been identified as 6 alpha-hydroxy-3-oxochol-4-ene-24-oic acid whilst the major neutral product has been identified as 6 alpha-hydroxyandrosta-1,4-diene-3,17-dione. The minor acidic products were 3,6-dioxochola-1,4-diene-24-oic acid, 3-oxochol-5-ene-24-oic acid, 3-oxochol-4-ene-24-oic acid, 3-oxochola-1,4-diene-24-oic acid and 6 alpha-hydroxy-3-oxochola-1,4-diene-24-oic acid and the minor neutral products were androst-4-ene-3,17-dione, androst-4-ene-3,6,17-trione, androsta-1,4-diene-3,6,17-trione, androsta-1,4-diene-3,17-dione, 17 beta-hydroxyandrosta-1,4-diene-3-one and 6 alpha-hydroxyandrost-4-ene-3,17-dione. Evidence is presented which suggests that under aerobic conditions, one pathway of hyodeoxycholic acid metabolism exists whilst under anaerobic conditions an extra biotransformation pathway becomes operative involving the induction of a 6 alpha-dehydroxylase enzyme. A biochemical pathway of hyodeoxycholic acid metabolism by bacteria under anaerobic conditions is discussed incorporating a scheme involving such an enzyme.     

Diterpene resin acids from the needle oleoresin of pinus strobus

The resin acid components of P. strobus needles were isolated, and the major constituents identified as labdenoic diterpenes. In addition to anticopalic and strobic acids previously reported in the needles, 3-oxoanticopalic, 3β-acetoxyanticopalic, 3β-hydroxyanticopalic acids and the 8α-hydroxy derivative of anticopalic acid were found along with two new compounds. The structures of the two new compounds, a cycloanticopalic acid and an abcoanticopalic acid, were determined by NMR. The composition of the diterpene resin acids was obtained for several samples of P. strobus needles from provenance tests.     

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.     

Ent-kaurane derivatives from the root cortex of yacon and other three Smallanthus species (Heliantheae,Asteraceae)

The metabolites produced by the secretory canals of the root cortex from four Smallanthus species belonging to the yacon group were identified as ent-kaurane-type diterpenes. The dichloromethane root cortex extracts of the four species were treated with diazomethane and analyzed comparatively by GC–MS using a simple and rapid procedure which is very sensitive and reproducible permitting detection of minor components. In all cases, ent-16-kauren-19-oic acid (kaurenoic acid) methyl ester was the main component, differences being observed only in the minor components. The minor components identified were grandiflorenic acid methyl ester, ent-16-kauren-19-al, 16α,17-epoxy-15α-angeloyloxy-kauran-19-oic acid methyl ester and several O-acyl derivatives at C-15 or C-18 of kaurenoic acid. One of the minor components, 18-isobutyroyloxy-ent-kaur-16-en-19-oic acid is a new kaurenoic acid derivative. Grandiflorenic acid and 15-α-angeloyloxy-16,17-α-epoxy-ent-16-kauren-19-oic acid were present only in Smallanthus sonchifolius and Smallanthus siegesbeckius which showed very similar GC traces. The different GC profile of RC diterpenes from Smallanthus connatus and Smallanthus macroscyphus supports the view that they are different taxa. Some chemotaxonomic aspects of the genus Smallanthus and the subtribe Milleriinae are briefly discussed.     

Formation of novel C21-bile acids from cholesterol in the rat. Structure identification of the major Di- and trihydroxylated species

We recently showed that previously unknown di- and trihydroxylated C21-bile acids are major degradation products of sitosterol and campesterol in bile-fistulated female Wistar rats. Using a mixture of 4-14C- and 22-3H-labeled cholesterol it was shown that such C21-bile acids are formed also from cholesterol in amounts up to about 25% of the total formation of bile acids. The C21-bile acids were formed from labeled cholesterol also in perfused rat liver, demonstrating that the liver is the site of synthesis. The major trihydroxylated C21-bile acids in bile were identified, by means of mass spectrometry, NMR, stereospecific dehydrogenases, and reagents, as 5 beta-pregnan-3 alpha, 11 beta, 15 beta-triol-21-oic acid and 5 beta-pregnan-3 alpha, 11 beta, 15 alpha-triol-21-oic acid. The corresponding 11-oxo-isomers were also present. A minor trihydroxylated C21-bile acid was identified as 5 beta-pregnan-3 alpha, 11 beta, 16-triol-21-oic acid. The major dihydroxylated C21-bile acid was identified by the same means as 5 alpha-pregnan-3 alpha, 12 alpha-diol-21-oic acid. Male rats converted 4-14C-cholesterol into C21-bile acids less efficiently than did female rats. None of the C21-bile acids from male rats contained a 15-hydroxyl group. It is speculated that the novel C21-bile acids are formed both from cholesterol and from plant sterols by an initial hydroxylation at C21 followed by peroxisomal or mitochondrial beta-oxidation. The presence of a hydroxyl group at C15 may facilitate this reaction. The above formation of C21-bile acids shows that mammalian liver is able to degrade the side chain of cholesterol beyond the C24 stage, even in the absence of a blocking group at C24. C21-bile acids, or one of their precursors, are hydroxylated in the liver by a hitherto unknown 11 beta-hydroxylase. The possible physiological importance of the C21-bile acids is discussed.     

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.     

Kolavane and kaurane diterpenes from the stem bark of Xylopia aethiopica

The stem bark of Xylopia aethiopica has yielded four diterpenes, two of them novel. Three of the diterpenes were identified as (?)-kaur-16-en-19-oic acid and its 7-oxo and 7β-hydroxy derivatives. The fourth was the novel kolavane derivative 2-oxo-kolav-3,13-dien-15-oic acid, a type of compound not previously recorded in the Annonaceae.     

Identification of 9,17-Dioxo-1,2,3,4,10,19-Hexanorandrostan-5-oic Acid, 4-Hydroxy-2-Oxohexanoic Acid, and 2-Hydroxyhexa-2,4-Dienoic Acid and Related Enzymes Involved in Testosterone Degradation in Comamonas testosteroni TA441

Comamonas testosteroni TA441 utilizes testosterone via aromatization of the A ring followed by meta-cleavage of the ring. The product of the meta-cleavage reaction, 4,5-9,10-diseco-3-hydroxy-5,9,17-trioxoandrosta-1(10),2-dien-4-oic acid, is degraded by a hydrolase, TesD. We directly isolated and identified two products of TesD as 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid and (2Z,4Z)-2-hydroxyhexa-2,4-dienoic acid. The latter was a pure 4Z isomer. 2-Hydroxyhexa-2,4-dienoic acid was converted by a hydratase, TesE, and the product isolated from the reaction solution was identified as 2-hydroxy-4-hex-2-enolactone, indicating the direct product of TesE to be 4-hydroxy-2-oxohexanoic acid.     

Dammarane triterpenes from Cabralea canjerana (Vell.) Mart. (Meliaceae): Their chemosystematic significance

The stem of Cabralea canjerana (Vell.) Mart. yielded three new dammarane triterpenes 20S,24S-epoxy-7β,25-dihydroxy-3,4-secodammar-4(28)-en-3-oic acid, 20S,24S-epoxy-7β,15α,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid and 20S,24R-epoxy-7β,22ξ,25-trihydroxy-3,4-secodammar-4(28)-en-3-oic acid, which were identified on the basis of spectroscopic methods. The known dammarane triterpenes ocotillone, eichlerianic acid, shoreic acid and the sterols sitosterol, campesterol, stigmasterol, sitostenone and stigmast-5-en-3-one were also isolated and identified. The branches yielded the above three known dammaranes and eichlerialactone. The dammaranes in C. canjerana display strong similarities with Trichilieae tribe, which contains several dammaranes. The data reported herein thus provide firm support for placing Cabralea within the subfamily Melioideae, Trichilieae tribe.     

Tricyclic diterpenes from the resin of Daemonorops draco and their activities on oxidative stress-induced mesenchymal stromal cells

A bioassay-guided chemical investigation of the resin exudates from Daemonorops draco (dragon’s blood, Palmaceae) has resulted in the isolation of two new trinorditerpenes, 7β-13-dihydroxypodocarpa-8,11,13-trien-15-oic acid (1) and 7α-13-dihydroxypodocarpa-8,11,13-trien-15-oic acid (2), along with ten previously described abietane diterpenes, 7β-15-dihydroxydehydroabietic acid (3), 7α-15-dihydroxydehydroabietic acid (4), 15-hydroxydehydroabietic acid (5), 7-oxodehydroabietic acid (6), dehydroabietic acid (7), 15-hydroxyabietic acid (8), 12α-hydroxyabietic acid (9), abietic acid (10), 7,13,15-abietatrien-18-oic acid (11), and cephasinene B (12). The structures of 1 and 2 were elucidated using spectroscopic techniques, including HR-ESIMS and 1D/2D NMR. The absolute configurations were determined by comparing the experimental electronic circular dichroism (ECD) spectra with the calculated ECD data based on time-dependent density functional theory. The bioactivity of the extracts, fractions, and isolated compounds was assessed in oxidative stress-induced mesenchymal stromal cells (MSCs). The crude extract and the hexanes, ethyl acetate, and aqueous fractions exhibited high potency against oxidative stress-induced apoptosis of MSCs. Among the isolated compounds, compounds 1 (3 μM) and 10 (100 μM) demonstrated good recovery of MSCs against oxidative stress.     

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.     

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.