Two new isodrimene sesquiterpenes from the fungal culture broth of Polyporus arcularius

Two new isodrimene sesquiterpene derivatives, 2(S)-hydroxyalbicanol (1, =(2S,4aS,8S,8aS)-8-(hydroxymethyl)-4,4,8a-trimethyl-7-methylenedecahydronaphthalen-2-ol) and 2(S)-hydroxyalbicanol 11-acetate (2, =((1S,4aS,7S,8aS)-7-hydroxy-5,5,8a-trimethyl-2-methylenedecahydronaphthalen-1-yl)methyl acetate) were isolated from the culture broth of the fungus Polyporus arcularius, together with two phenylpropanediols, (1S,2S)- and (1R,2S)-1-phenyl-1,2-dihydroxypropane (3, 4). Compound 3 is reported as a naturally occurring compound for the first time. The structures of the compounds were elucidated on the basis of spectroscopic analysis. Compound 1 exhibited growth inhibition of lettuce seedlings with IC₅₀ values of 1.3 mM to hypocotyl and 1.7 mM to radicle.     

Flavans and other chemical constituents of Crinum biflorum (Amaryllidaceae)

The ethyl acetate extract from the whole plant of Crinum biflorum Rottb. Showed a moderate activity against Enterococcus faecalis. Its phytochemical investigation led to the isolation of a new flavan-3-ol derivative namely (2R,3R)-3-hydroxy-7-methoxy-3′,4′-methylenedioxyflavan, together with (2S)-7-hydroxy-3′,4′-methylenedioxyflavan, (2R,3R)-7-methoxy-flavan-3-ol, (2S)-7-hydroxy-3′,4′-dimethoxyflavan, 3′,7-dihydroxy-4′-methoxyflavan, 4′,7-dimethoxy-3′-hydroxyflavan, farrerol, β-sitosterol, β-sitosterol-3-O-β-D-glucopyranoside, oleanolic acid, kaempferol, pancratistatin, lupeol, aurantiamide acetate, Narciprimine and 2,3-dihydroxypropyl palmitate. Their structures were elucidated mainly by extensive spectroscopic analysis and comparison with published data. The absolute configuration of the new metabolite was determined by electronic circular dichroism (ECD) analysis and comparison of optical rotation. Some of the isolated compounds were tested for their antimicrobial activity but no inhibition was observed.     

Regulation of cholesterol biosynthesis and metabolism in Hep G2 cells by Δ8(14)-15-ketoergostane derivatives

The comparative study of effects of 5α-cholest-8(14)-en-15-on-3β-ol (I), (22E)-5α-ergosta-8(14),22-dien-15-on-3β-ol (II), (22S,23S)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (III), and (22R,23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) on HMG-CoA reductase, CYP27A1 and CYP3A4 genes expression in Hep G2 cells was performed. In the contrast to the 15-ketocholestane derivative (I), 15-ketoergostane derivatives (II–IV) decreased the HMG-CoA reductase mRNA level; (22R, 23R)-22,23-oxido-5α-ergost-8(14)-en-15-on-3β-ol (IV) significantly increased CYP3A4 mRNA level (320% from control). Ketosterol (II) was found to be a more potent inhibitor of cholesterol biosynthesis in Hep G2 cells during prolonged incubation, compared with ketosterol (I). The side chain conformation of compounds (I)–(IV) was evaluated by computational modeling; the correlation between biological activity of these compounds and conformational flexibility of their side chains was found. The results obtained indicate that Δ8(14)-15-ketoergostane derivatives may be used as a sterol biosynthesis and metabolism regulators in liver cells.     

Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii

Strophasterols E (1) and F (2) were isolated from the fruiting bodies of Pleurotus eryngii, together with four new ergostane-type sterols (3–6). Single-crystal X-ray diffraction analysis performed on the tris-p-bromobenzoate derivatives of compounds 1 and 2 allowed these two compounds to be identified as the structurally rare (22S,23R)- and (22S,23S)-5α,6α-epoxy-3β,7β,23-trihydroxy-15(14 → 22)-abeo-ergost-8-en-14-one, respectively. The inhibitory effects on nitric oxide production of the six new steroids thus isolated from the fruiting bodies of P. eryngii were also evaluated.     

Triterpenoids from the African tree Phyllanthus polyanthus

The stem bark of Phyllanthus polyanthus (Phyllanthaceae) has yielded phyllanthol, phyllanthone, (20S)-3β-acetoxy-24-methylenedammaran-20-ol, δ-amyrin acetate and lupenone and the leaves yielded (20S)-3α-acetoxy-24-methylenedammaran-20-ol. NMR data for phyllanthol provided in the literature have been revised.     

β-Resorcylic Acid Derivatives,with Their Phytotoxic Activities,from the Endophytic Fungus Lasiodiplodia theobromae in the Mangrove Plant Xylocarpus granatum

Nine new β-resorcylic acid derivatives, (15S)-de-O-methyllasiodiplodin ( 1 ), (13S,15S)-13-hydroxy-de-O-methyllasiodiplodin ( 2 ), (14S,15S)-14-hydroxy-de-O-methyllasiodiplodin ( 3 ), (13R,14S,15S)-13,14-dihydroxy-de-O-methyllasiodiplodin ( 4 ), ethyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate ( 5 ), ethyl 2,4-dihydroxy-6-(8-hydroxyheptyl)benzoate ( 6 ), ethyl 2,4-dihydroxy-6-(4-methoxycarbonylbutyl)benzoate ( 7 ), 3-(2-ethoxycarbonyl-3,5-dihydroxyphenyl)propionic acid ( 8 ), and isobutyl (S)-2,4-dihydroxy-6-(8-hydroxynonyl)benzoate ( 9 ), together with a known ethyl 2,4-dihydroxy-6-(8-oxononyl)benzoate ( 10 ) were obtained from Lasiodiplodia theobromae GC-22. The structures of these compounds were elucidated by extensive spectroscopic analyses. Compounds 1 , 3 , and 6 showed growth inhibitory effects against Digitaria ciliaris. Conversely, treatment with compounds 5 , 6 , 7 , 9 , and 10 stimulated elongation activity toward the root of Lactuca sativa. These data expand the repertoire of new β-resorcylic acid derivatives that may function as lead compounds in the synthesis of new agrochemical agents.     

The conversion of (24S)-24-ethylcholesta-5,22,25-trien-3β-ol into poriferasterol,both in vivo and with a cell-free homogenate of the alga Trebouxia sp.

[6-³H₁] (24S)-24-Ethylcholesta-5,22,25-trien-3β-ol added to the growth medium of a culture of Trebouxia sp. 213/3 was efficiently taken-up by the cells and converted into (24R)-24-ethylcholesta-5,22-dien-3β-ol (poriferasterol) which is one of the major sterols of this alga. A cell-free homogenate was obtained from Trebouxia which catalysed the NADPH-dependent reduction of [6-³H₁] (24S)-24-ethylcholesta-5,22,25-trien-3β-ol to yield poriferasterol. The δ²⁵-sterol reductase was found to be mainly localized in the microsomal fraction of the homogenate.     

Configurational studies on red algae carotenoids

The configurations of (6′R)-β,ε-carotene, (3′R,6′R)-β,ε-caroten-3′-ol (α-cryptoxanthin), (3R,3′R,6′R)-β,ε-carotene-3,3′-diol (lutein), (3R)-β,β-caroten-3-ol (β-cryptoxanthin), (3R,3′R)-β,β-carotene-3,3′-diol (zeaxanthin) and all-trans (3S,5R,6S,3′R)-5,6-epoxy-5,6-dihydro-β,β-carotene-3,3′-diol (antheraxanthin) were established by CD and ¹H NMR studies. The red algal carotenoids consequently possessed chiralities at each chiral center (C-3, C-5, C-6, C-3′, C-6′), corresponding to the chiralities established for the same carotenoids in higher plants. Two post mortem artifacts from Erythrotrichia carnea were assigned the chiral structures (3S,5R,8R,3′R)-5,8-epoxy-5,8-dihydro-β,β-carotene-3,3′-diol [(8R)-mutatoxanthin] and (3S,5R,8S,3′R)-5,8-epoxy-5,8-dihydro-β,β-carotene-3,3′-diol [(8S)-mutatoxanthin]. This is the first well documented report of a naturally occurring β,ε-caroten-3′-ol (¹H NMR, CD, chemical derivatization).     

Reactions of ethyl 3,5,6-tri-O-acetyl-2-S-ethyl-1,2-dithio-α-D-mannofuranoside with halogens

Ethyl 3,5,6-tri-O-acetyl-2-S-ethyl-1,2-dithio-α-D-mannofuranoside (5) reacted with bromine to give the very unstable glycosyl bromide 4, which with water gave a mixture of the 1-hydroxyl analogue (8) and the nonreducing α-D-(1→1)-linked disaccharide derivative 9. When the bromide 4 was treated with mercuric acetate or potassium acetate, 1,3,5,6-tetra-O-acetyl-2-S-ethyl-2-thio-α-D-mannofuranose (7) was obtained, but silver acetate in carbon tetrachloride gave 7 in admixture with its β-anomer (10). Methanol reacted with 4 to give an anomeric mixture of the glycofuranosides (11 and 12). An excess of chlorine converted the dithio derivative 5 into a 3,5,6-tri-O-acetyl-2-chloro-2-S-ethyl-2-thio-D-manno(or gluco)furanosyl chloride (13), whereas a lower proportion of chlorine appeared to give the 1-chloro analogue of 4. Treatment of the dichloro derivative 13 with methanol led to a mixture of three methyl glycosides, one (14) retaining the chlorine atom at C-2, and the other two (15 and 16) resulting from exchange of both chlorine atoms by methoxyl groups.     

Oligofuro- and spiro-stanosides of Asparagus adscendens

Two oligofurostanosides and two spirostanosides, isolated from a methanol extract of Asparagus adscendens (leaves), were characterized as 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]-22α-methoxy-(25S)-furost-5-en-3β,26-diol (Adscendoside A), 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]-(25S)-furost-5-en-3β,22α,26-triol-(Adscendoside B), 3-O-[{α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyranosyl]-(25S)-spirostan-5-en-3β-ol (Adscendin A) and 3-O-[{α-l-rhamnopyranosyl (1 → 4)} {α-l-rhamnopyranosyl (1 → 6)}-β-d-glucopyr anosyl]-(25S)-spirostan-5-en-3β-ol (Adscendin B), respectively. Adscendin B and Adscendoside A are the artefacts of Adscendoside B formed through hydrolysis and methanol extraction respectively.bl]     

Three squalene derivatives from Caulerpa prolifera

(6S,7S)-Squalene-6,7-epoxide, (10S, 11S)-squalene-10,11-epoxide and all-trans-(3S)-2,6,10,15,19,23-hexamethyltetracosa-1,6,10,14,18,22-hexaen-3-ol have been isolated from the marine alga Caulerpa prolifera.     

Sterols with unusual nuclear unsaturation from three cultured marine dinoflagellates

Several new 4α-methyl sterols with unusual unsaturation in the Δ⁸⁽¹⁴⁾-or Δ¹⁴-positions, 4α,24S-dimethyl-5α-cholest-8 (14)-en-3β-ol, 4α-methyl-24ξ-ethyl-5α-cholest-8(14)-en-3β-ol, 4α-methyl-24(Z)-ethylidene-5α-cholest-8(14)- en-3β-ol, 4α,23 (or 22),24ξ-trimethyl-5α-cholesta-8(14),22-dien-3β-ol, 4α,24S(or 23ξ)-dimethyl-5α-cholest-14-en-3β-ol and 14-dehydrodinosterol, have been isolated from extracts of the cultured marine dinoflagellates Amphidinium carterae, A. corpulentum and Glenodinium sp. 4α-Methyl-24ξ-ethyl-5α-cholestan-3β-ol was isolated from the steryl ester fraction of Glenodinium sp. The structures of these new sterols are based upon extensive 360 MHz ¹H NMR and MS analyses.     

Steroidal saponins of Asparagus curillus

Three spirostanol and two furostanol glycosides were isolated from a methanol extract of the roots of Asparagus curillus and characterized as 3-O-[α-l-arabinopyranosyl (1→4)- β-d-glucopyranosyl]-(25S)-5β-spirostan-3β-ol, 3-O-[{α-l-rhamnopyranosyl (1→2)} {α-l-arabinopyranosyl (1→4)}-β-d-glucopyranosyl]-(25S)-5β-spirostan- 3β-ol, 3-O-[{β-d-glucopyranosyl (1→2)} {α-l-arabinopyranosyl (1→4)}-β- d-glucopyranosyl]-(25S)-5β-spirostan-3β-ol, 3-O-[{β-d-glucopyranosyl (1→2)} {α-l-arabinopyranosyl (1→4)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]- 22α-methoxy-(25S)-5β-furostan-3β, 26-diol and 3-O-[{β-d-glucopyranosyl (1→2)} {α-l-arabinopyranosyl (1→4)}-β-d-glucopyranosyl]-26-O-[β-d-glucopyranosyl]- (25S)-5β-furostan-3β, 22α, 26-triol respectively.     

Concerning the biosynthesis of prostaglandin I2

Two diastereoisomers, 5R,6R-5-hydroxy-6(9α)-oxido-11α,15S-dihydroxyprost-13-enoic acid (7) and 5S,6S-5-hydroxy-6(9α)-oxido-11α,15S-dihydroxyprost-13-enoic acid (10) were synthesized for evaluation as possible biosynthetic intermediates in the enzymatic transformation of PGH₂ or PGG₂ into PGI₂. The synthetic sequence entails the stereospecific reduction of the 9-keto function in PGE₂ methyl ester after protecting the C-11 and C-15 hydroxyls as tbutyldimethylsilyl ethers. The resulting PGF_2α derivative was epoxidized exclusively at the C-5 (6) double bond to yield a mixture of epoxides, which underwent facile rearrangement with SiO₂ to yield the 5S,6S and 5R,6R-5-hydroxy-6(9α)-oxido cyclic ethers. It was found that dog aortic microsomes were unable to transform radioactive 9β-5S,6S[³H] or 9β-5R,6R[³H]-5-hydroxy-6(9α)-oxido cyclic ethers into PGI₂. Also, when either diastereoisomer was included in the incubation mixture, neither isomer diluted the conversion of [1-¹⁴C]arachidonic acid into [1-¹⁴C]PGI₂.     

Volatile oil constituents of sagebrush

The volatile oil of Artemisia arbuscula arbuscula contained a new irregular monoterpene, 2,5-dimethyl-4-vinyl-1,5-hexadiene-3-ol (isolyratol), which was isolated and identified by spectral means. The optically pure furanoid (2S,5S)-trans-5-methyl-5-vinyltetrahydrofur-2-yl methyl ketone (arbusculone), was also characterized by transformation to known (2S,5S)-trans-linalyl oxide. The former component has never been isolated from natural sources prior to this study. The neutral pentane extract also contained several previously characterized non-head-to-tail monoterpenes including artemiseole, artemisia ketone, artemisyl acetate, methyl santolinate, and santolina triene, as well as the regular monoterpenes 1,8-cineole, camphor, p-cymene, camphene and the C₆ fragment, terelactone.     

Tetraludin A,B and C,three new melampolides from Tetragonotheca ludoviciana

The investigation of the roots of the four Tetragonotheca species, T. ludoviciana, T. repanda, T. texana and T. helianthoides, resulted in the isolation of the known heptadeca-2-(Z)-8,10-(E)-16-tetraene-4,6-diin-1-ol and its aldehyde derivative from all four species. Aerial parts of T. ludoviciana also contained the acetate of the latter compound as a minor constituent and provided three new melampolide-type sesquiterpene lactones, tetraludin A, B and C.     

The absolute configuration of the new amino acid 2-amino-4-methyl-hex-5-enoic acid from a new guinea Boletus

The absolute configuration of the 2-amino-4-methyl-hex-5-enoic acid isolated from Boletus was shown to be 2S, 4S, by an unambiguous synthesis of its dihydro derivative from 2S-(?)-2-methylbutan-1-ol.     

Microbial hydroxylation of chiral bicyclic enones by Chaetomium sp.1 and Didymosphaeria igniaria cultures

The biotransformations of (R)-(?)-methyloctalone and (S)-(+)-methyloctalone were investigated using Chaetomium sp.1 KCH 6651 and Didymosphaeria igniaria KCH 6670 as biocatalysts, yielding mostly 6β- and 7β-hydroxy derivatives. During the incubation of (R)-methyloctalone with the Chaetomium sp.1 culture, three products were obtained: the trans-7β-hydroxy derivative in 50% yield, trans-6β-hydroxy derivative in 30% yield and cis-8α-hydroxy derivative in 6% yield. The (S)-enone was hydroxylated mainly in the 6α-position (with 60% yield). 6β- and 7β-hydroxy derivatives are new compounds, not previously described in the literature. The biotransformation of the two enantiomers of methyloctalone with D. igniaria also afforded monohydroxy derivatives. In both cases the main product of transformation was the allylic hydroxy derivative (27–35% yield). D. igniaria transformed the (R)-methyloctalone more rapidly whereas Chaetomium sp. 1 preferred the (S)-methyloctalone.     

Sphingosine derivatives from red algae of the ceramiales

(+)-2(S)-N-Acetamido-3(R)-acetoxyoctadecan-1-ol, a diacetate of dihydrosphingosine, and fatty acid amides of (?)-2(S)-amino-3(R)-hydroxyoctadec-4(E)-en-1-ol (sphingosine) have been isolated from extracts of Hawaiian Laurencia nidifica and Amansia glomerata, respectively. Although well known as constituents of nerve tissue hydrolyzates throughout the animal kingdom, these compounds have not been previously found in plants.     

Lipase-Catalyzed Kinetic Resolution of (±)-cis-Flavan-4-ol and Its Acetate: Synthesis of Chiral 3-Hydroxyflavanones

Lipase-catalyzed kinetic resolution of (±)-cis-flavan-4-ol and its acetate led to enantiomerically enriched flavan-4-ol and its acetate. These chiral compounds were converted to (2R, 3R)- and (2S, 3S)-3-hydroxyflavanones.