Identification de stérols à chaîne latérale oxygénée dans une éponge de l'espèce Hyrtios

Thirty-two sterols are identified in the sponge Hyrtios sp. In addition to fourteen monohydroxylated compounds, the sterol fraction contains eight functionalized sidechain sterols, three of them new: 3 β-hydroxy-24-norchol-5-en-23-al (19) , (22-trans)-3 β-hydroxycholest-5, 22-dien-24-one (20) and (22R, 23R, 24S) or (22S, 23S, 24S)- 22,23-epoxy-24-methylchoest-5-en-3 β-ol (24). The probable biological origin, rather than artifact production, of these undescribed components is discussed.     

Sterol sulfates from the Far Eastern holothurianCucumaria japonica

A chloroform-methanol extract of the musculocutaneous sac of the Far-Eastern holothurianC. japonica has yielded a fraction of sterol sulfates (13% of the weight of the extract, 0.8% of the weight of the dry biomass), the main components of which were derivatives of cholest-5-en-3β-ol, 24-methylene-, 24-ethyl-, and 24-ethylidenecholest-5-en-3β-ols, 5α-cholestan-3β-ol, and 24-methyl- and 24-methylene-5α-cholesten-3β-ol; among the minor components were found the sulfates of 24-ethyl-5α-cholestan-3β-ol of cholesta-5,22-dien-3β-ol, of a Δ⁵-C₃₀ sterol, and also of dienic and trienic C₂₆ sterols.     

Steroid alcohols from the ascidianHalocynthia aurantium

The total sterols have been isolated fromHalocynthia aurantium by column chromatography on silica gel. The following steroid alcohols have been identified in it with the aid of GLC, GLC-MS, and¹H NMR: 5α-cholestan-3β-ol, 24ξ-methylcholestan-3β-ol, 24ξ-ethylcholestan-3β-ol, 4ξ-methyl-24ξ-ethyl-5α-cholestan-3β-ol, cholest-5-en-3β-ol, 24ξ-methylcholest-5-en-3β-ol, 24ξ-ethylcholes-5-en-3β-ol, 5α-cholest-22-en-3β-ol, 24-nor-5α-cholest-22-en-3β-ol, cholesta-5,22-dien-3β-ol, 24ξ-methylcholesta-5,22-dien-3β-ol, 24-norcholesta-5,22-dien-3β-ol, 24-ethylcholesta-5,24(28)-dien-3β-ol, and 24-methylcholesta-5,24(28)-dien-3β-ol.     

Isolation,Structure Determination and Synthesis of New Acetylenic Steroids from the Sponge Calyx nicaaensis

Two acetylenic steroids, cholest-5-en-23-yn-3β-ol ( 5 ) and 26,27-dinorcholest-5-en-23-yn-3β-ol ( 3 ), and another unsaturated steroidalcohol, stigmasta-5,23-dien-3β-ol ( 7 ), were isolated from the sponge Calyx nicaaensis. The structures of these two acetylenic steroids were established by synthesis. Several attempts to synthesize the marine steroids alcohol calysterol ( 1 ), with a cyclopropene-containing side chain, starting from cholest-5-en-23-yn-3β-ol are also recorded. Addition of ethyl-diazo-acetate to the triple bond was performed, but the reduction to the methyl derivative yielded decomposition products.     

Use of n-lithioethylenediamine in the double bond isomerization and degradation of sterol side chains

Double bond isomerization of stigmasterol ((24S)-24-ethylcholesta-5,22-dien-3β-ol) with N-lithioethy-lenediamine produced stigmasta-5,17(20)-dien-3β-ol, stigmasta-5,20(22)-dien-3β-ol, stigmasta-5,23-dien-3β-ol and stigmasta-5,24-dien-3β-ol. Some starting material was also present in the isomerization mixture along with a small amount of stigmast-5-en-3β-ol. Similar treatment of 3α,5-cyclo-6β-methoxystigmast-22-en (stigmasterol i-methyl ether) followed by ozonization and removal of the ring A-protecting group yielded predominantly 3β-hydroxy-androst-5-en-17-one and 3β-hydroxypregn-5-en-20-one. The isomerization products of fucosterol (24-ethylcholesta- 5, 24(28)E-dien-3β-ol) and 23,24-bisnorchola-5,20-dien-3β-ol are also reported.     

20, 21-Azirdin-Steroide: Reaktion von Derivaten der Oxime von 5-Pregnen-20-on,9β,10α-5-Pregnen-20-on und 9β,10α-5,7-Pregnadien-20-on mit Lithiumaluminiumhydrid und von 3β-Hydroxy-5-pregnen-20-on-oxim mit Grignard-Verbindungen

20, 21-Aziridine Steroids: Reaction of Derivatives of the Oximes of 5-Pregnen-20-one, 9β, 10α-5-Pregnen-20-one and 9β, 10α-5,7-Pregnadiene-20-one with Lithium Aluminium Hydride, and of 3β-Hydroxy-5-pregnen-20-one Oxime with Grignard Reagents. Reduction of 3β-hydroxy-5-pregnen-20-one oxime ( 2 ) with LiAlH₄ in tetrahydrofuran yielded 20α-amino-5-pregnen-3β-ol ( 1 ), 20β-amino-5-pregnen-3β-ol ( 3 ), 20β, 21-imino-5-pregnen-3β-ol ( 6 ) and 20β, 21-imino-5-pregnen-3β-ol ( 9 ). The aziridines 6 and 9 were separated via the acetyl derivatives 7 and 10 . The reaction of 6 and 9 with CS₂ gave 5-(3β-hydroxy-5-androsten-17β-yl)-thiazolidine-2-thione ( 8 ). Treatment of the 20-oximes 12 and 15 of the corresponding 9β,10α(retro)-pregnane derivatives with LiAlH₄ gave the aziridines 13 and 16 , respectively. Their deamination led to the diene 14 and triene 17 , respectively. Reduction of isobutyl methyl ketone-oxime with LiAlH₄ in tetrahydrofuran yielded 2-amino-4-methyl-pentane ( 19 ) as main product, 1, 2-imino-4-methyl-pentane ( 22 ) as second product and the epimeric 2,3-imino-4-methyl-pentanes 20 and 21 as minor products. – 3β-Hydroxy-5-pregnen-20-one oxime ( 2 ) was transformed by methylmagnesium iodide in toluene to 20α, 21-imino-20-methyl-5-pregnen-3β-ol ( 23 ) and 20β, 21-imino-20-methyl-5-pregnen-3β-ol ( 26 ). Acetylation of these aziridines was accompanied by elimination reactions leading to 3β-acetoxy-20-methylidene-21-N-acetylamino-5-pregnene ( 30 ) and 3β-acetoxy-20-methyl-21-N-acetylamino-5,17-pregnadiene ( 32 ). The reaction of oxime 2 with ethylmagnesium bromide in toluene gave 20α, 21-imino-20-ethyl-5-pregnen-3β-ol ( 24 ) and 20α,21-imino-20-ethyl-5-pregnen-3β-ol ( 27 ). Acetylation of 24 and 27 led to 3β-acetoxy-20-ethylidene-21-N-acetylamino-5-pregnene ( 31 ), 3β-acetoxy-20-ethyl-21-N-acetylamino-5,17-pregnadiene 33 and 3β, 20-diacetoxy-20-ethyl-21-N-acetylamino-5-pregnene ( 37 ). With phenylmagnesium bromide in toluene the oxime 2 was transformed to 20β, 21-imino-20-phenyl-5-pregnen-3β-ol ( 25 ) and 20β,21-imino-20-phenyl-5-pregnen-3β-ol ( 28 ). Acetylation of 25 and 28 yielded 3β-acetoxy-20-phenyl-21-N-acetylamino-5, 17-pregnadiene ( 34 ) and 3β,20-diacetoxy-20-phenyl-21-N-acetylamino-5-pregnene ( 39 ). LiAlH₄-reduction of 39 gave 3β, 20-dihydroxy-20-phenyl-21-N-ethylamino-5-pregnene ( 41 ). – The 20, 21-aziridines are stable to LiAlH₄. Consequently they are no intermediates in the formation of the 20-amino derivatives obtained from the oxime 2 .     

Conformational comparison of five follicular fluid meiosis-activating sterol-related active and inactive compounds

The crystal structures of five follicular fluid meiosis-activating sterol-related Δ^8,14-sterol compounds are presented. These are 4,4-di­methyl-23-phenyl-24-nor-5α-chola-8,14-dien-3β-ol, C₃₁H₄₄O, 4,4-di­methyl-22-phenyl-23,24-dinor-5α-chola-8,14-dien-3β-ol, C₃₀H₄₂O, (20R)-4,4-di­methyl-22-oxa-5α,20-chol­es­ta-8,14,24-trien-3β-ol, C₂₈H₄₄O₂, 4,4-di­methyl-23-phenyl-22-oxa-24-nor-5α-chola-8,14-dien-3β-ol–water (4/1), 4C₃₀H₄₂O₂·H₂O, and 4,4-di­methyl-5α-cholesta-8,14-dien-3-one, C₂₉H₄₆O. Two of the derivatives are inactive and three are active as agonists. Preliminary structure–activity relationship studies showed that the positions of the double bonds in the skeleton and the structures of the side chains are important determinants for activity. The conformations of the skeletons were compared with double-bond isomers retrieved from the Cambridge Structural Database [Allen & Kennard (1993). Chem. Des. Autom. News, 8 , 1, 31–37]; no significant differences were found. Thus, conformational changes induced by the double bonds are not discriminative with respect to the activity of the compounds. Comparisons of the side-chain conformations of active and inactive structures revealed that the crystal structures were not conclusive as far as correlation of conformation and activity of the side chains were concerned.     

Minor and Trace Sterols in Marine Invertebrates. XII. Occurrence of 24 (R + S)-isopropenylcholesterol, 24 (R + S)-methylcholesta-5, 25-dien-3β-ol,and 24 (R + S)-methylcholesta-7, 25-dien-3β-ol in the caribbean sponge,Verongia cauliformis

In addition to the two new sterols verongulasterol 11 and 25-dehydroaplysterol 13 of Verongia cauliformis³), which were reported earlier [2] [3], the minor and trace sterols of this sponge include five new sterols listed in the title (with the exception of the known 24 S-methyl-cholesta-5, 25-dien-3β-ol (codisterol, 1b ). The isolation of the 24(R)-epimer of codisterol is of interest, as this compound is a possibly biosynthetic precursor for aplysterol 12 , 25-dehydroaplysterol 13 , and verongulasterol 11 (all 24R) which occur in the same sponge [2]. A partial synthesis from fucosterol ( 4 ) of 24 (R + S)-isopropenylcholesterol ( 9 ), and of 24-isopropylcholesterol ( 10 ) is described.     

On the First Marine Stigmastane Sterols and Sterones Having a 24,25-Double Bond. Isolation from the Sponge Stelletta sp. of Deep Coral Sea

The sponge Stelletta sp. (Astrophorida, Stellettidae), collected at ?700 m in the Coral Sea, is shown to contain sterones and sterols of the stigmastane type with a C(24)?C(25) bond for which there is no precedent in the sea. Structure elucidation of the second abundant of these steroids, stigmasta-4,24(25)-dien-3-one ((+)- 1 ), is based on 1D and 2D NMR spectra and chemical transformation to acetate (?)- 5 . Stigmasta-4,24(25)-diene-3,6-dione ((?)- 3 ), present in trace amounts in the sponge, was obtained in sufficient quantity for NMR study by oxidation of the also present, inseparable, and abundant 4:1 mixture of stigmasta-5,24(25)-dien-3β-ol ( 6 ) and its 5,6-dihydro derivative 7 (Scheme 1). This oxidation also afforded the ketone analogues (+)- 8 and (+)- 9 , which could be separated, thus making structure elucidation possible. The 6β-hydroxystigmasta-4,24(25)-dien-3-one ((+)- 4 ), also present in trace amounts in the sponge, was obtained in sufficient amount for NMR study, together with its C(6) epimer (+)- 11 , by hydroperoxidation of (+)- 8 followed by deoxygenation (Scheme 2). The last trace steroid of the sponge, stigmasta-4,6,24(25)-trien-3-one ((?)- 2 ), was structurally elucidated using limited NMR data and comparison with the other stigmastanes. These stigmastanes, as the only steroids of this sponge, are likely to function as stabilizers of its cell walls; their phytosteroid structure, for a sponge which lives in the dark of deep waters, suggest origin through a complex food chain, possibly followed by bioelaboration in the sponge.     

Studies on the Constituents of Ganoderma Lucidum

The methanolic extract of fruit bodies of cultivated Ganoderma lucidum was separated by silica gel column chromatography and preparative thin-layer chromatography to give ten compounds. On the basis of spectral analysis, chemical procedures and gas chromatography, d-mannitol (1), ergosta-7, 22-dien-3β-yl palmitate (2), ergosterol (3), ergosta-7, 22-dien-3β-ol (4), 5α-lanosta-7,9(11),24-trien-3β,26-diol (5), ergosterol peroxide (6), 24,25,26-trihydroxy-5α-lanosta-7,9(11)-dien-3-one (7), 5α-lanosta-7,9(11)-dien-3β,24,25,26-tetraol (8) and 8,9-epoxyergosta-5,22-dien-3β,15-diol (9) were identified. Among these compounds, 8,9-epoxyergosta-5,22-dien-3β,15-diol was first separated from Ganoderma lucidum.     

The Neutral Part of the Bark of Pinus Taiwanensis Hayata

The neutral part of the acetone extract from the bark of Pinus taiwanensis Hayata has been Investigated and found to consist of alkanes (C₁₄-C₃₃), longifolene, aliphatic esters (C₄₂, C₄₄, C₄₉), aliphatic alcohols (C₂₄, C₂₆), 3β-21α-dimethoxyserrat-14-enc, 3β-methoxyserrat-14-en-21-one, β-sitosterol, 3β-methoxyserrat-14-en-21ã-ol and 3β-hydroxyserrat-14-en-21-one.     

Ergosta-5,7,9(11), 22-tetraen-3β-ol and its 24ξ-Ethyl Homolog,Two New Marine Sterols from the Red Sea Sponge Biemna fortis

The steroidal components of a Red Sea sponge, Biemna fortis, were fractionated through reversed phase HPLC. and analyzed by a combination of physical methods, including high resolution GC./MS. and 360 MHz ¹H-NMR. The sponge contains five conventional Δ⁵-sterols, 1a – c , 1e , 1g , which comprise about 25% of the mixture and 2,5% of gorgosterol (1h) , a sterol never found before in Porifera. Three Δ^5,7,22-sterols were also present as major components in the mixture (～70%): cholesta-5,7,22-trien-3β-ol (2a) , ergosta-5,7,22-trien-3β-ol (2c) and (24R)-ethylcholesta-5,7,22-trien-3β-ol (2e) whereas two new tetra-unsaturated sterols were identified in minor amounts (2%): ergosta-5,7,9(11),22-tetraen-3β-ol (3c) and 24ξ-ethylcholesta-5,7,9 (11), 22-tetraen-3β-ol ( 3e or 3f ). NMR. spectroscopy made possible the assignment of a 24R configuration for all the C(24) substituted sterols isolated in sufficient amount from the mixture. The possible symbiotic, dietary or biosynthetic origins of these sterols are discussed.     

Synthesis and screening of aromatase inhibitory activity of substituted C19 steroidal 17-oxime analogs

The synthesis and aromatase inhibitory activity of androst-4-en-, androst-5-en-, 1β,2β-epoxy- and/or androsta-4,6-dien-, 4β,5β-epoxyandrostane-, and 4-substituted androst-4-en-17-oxime derivatives are described. Inhibition activity of synthesized compounds was assessed using aromatase enzyme and [1β-3H]androstenedione as substrate. Most of the compounds displayed similar to or more aromatase inhibitory activity than formestane (74.2%). 4-Chloro-3β-hydroxy-4-androsten-17-one oxime (14, 93.8%) showed the highest activity, while 4-azido-3β-hydroxy-4-androsten-17-one oxime (17, 32.8%) showed the lowest inhibitory activity for aromatase.     

Two new epoxysteroids from Helianthus tuberosus

Two new epoxy steroids, 5α,8α-epidioxy-22β,23β-epoxyergosta-6-en-3β-ol (1) and 5α,8α-epidioxy-22α,23α-epoxyergosta-6-en-3β-ol (2), and ten known steroids including (24R)-5α,8α-epidioxyergosta-6-en-3β-ol (3), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (4), (22E,24R)-5α,8α-epidioxyergosta-6,9(11),22-trien-3β-ol (5), β-sitosterol (6), sitost-5-en-3β-ol acetate (7), 7α-hydroxysitosterol (8), schleicheol 2 (9), (24R)-24-ethyl-5α-cholestane-3β,5α,6β-triol (10), 7α-hydroxystigmasterol (11), and stigmasterol (12) were isolated from Helianthus tuberosus grown in Laizhou salinized land of coastal zone of Bohai Sea, China. The structures of these compounds were unambiguously established by 1D, 2D NMR and mass spectroscopic techniques. The new compounds 1 and 2 exhibited weak antibacterial activity and no antifungal activity.     

Face selectivity of the Diels-Alder additions and cheletropic additions of sulfur dioxide to 2- vinyl-7-oxabicyclo[2.2.1]hept-2-ene derivatives

Racemic 6-ethenyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 23 ), 5-ethenyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 25 ) and their ethylene acetals 24 and 26 , respectively, were derived from the Diels-Alder adduct of furan to 1-cyanovinyl acetate ( 27 ). The Diels-Alder additions of 26 to dimethyl acetylenedicarboxylate, to methyl propynoate, to N-phenylmaleimide, and to methyl acrylate were highly exo-face selective, as were the cycloadditions of methyl propynoate to dienones 23 and 25 and of dimethyl acetylenedicarboxylate to ethylenedioxy-diene 24 . The cheletropic additions of SO₂ to 23 – 26 gave exclusively the corresponding sulfolenes 57 – 60 resulting from the exo-face attack of the semicyclic dienes under conditions of kinetic and thermodynamic control.     

Synthesis of a transmembrane ionophore based on a C2-symmetric polyhydroxysteroid derivative

The synthesis of the C₂-symmetric bis-(20S)-5α-23,24-bisnorchol-16-en-3β,6α,7β-triol-22-terephthaloate (1), active as Na⁺-transporting transmembrane channel, has been achieved in 16 steps (10% overall yield) starting from the commercially available androst-5-en-3β-ol-17-one (3). The straightforward stereospecific functionalization of the side-chain, via the ‘ene’ reaction, and the successful regioselective terephthaloylation of the C-22 hydroxy group, illustrate the efficiency of the synthetic strategy.     

Marine sterols—II : Asterosterol,a new C26 sterol from Asterias amurensis lütken

Asterosterol, a new marine C₂₆ sterol, was isolated from the asteroid, A. amurensis, and its structure was characterized as 22-trans-24-nor-5α-cholesta-7,22-dien-3β-ol (1). Episterol (9), 22-trans-(24R)-24-methylcholesta-7,22-dien-3β-ol (stellasterol, 3) and 22-trans-cholesta-7,22-dien-3β-ol (7) were also isolated and their structures were confirmed.     

Polyoxygenated ergostane-type sterols from the liquid culture of Ganoderma applanatum

A new polyoxygenated ergostane-type sterol, 3β,5α,6β,8β,14α-pentahydroxy-(22E,24R)-ergost-22-en-7-one (1), has been isolated from the liquid culture of the basidiomycete Ganoderma applanatum together with four known sterols, 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2), ergosterol peroxide (3), 6-dehydrocerevisterol (4) and cerevisterol (5). Two of these sterols (2, 4) are reported to have been isolated from this species for the first time. The structures of these compounds were determined by chemical and spectroscopic analyses, including 1D- and 2D-NMR, as well as by comparison of their spectroscopic data with those reported in the literature.     

Constituents of Fruit Bodies of Tramete orientalis

A known sterol, 5α,6α-epoxy-5α-crgosta-8(14),22E-diene-3β,7α-diol ( 1 ), and two new sterols, 5α,6α-epoxy-3β,8β,14α-trihydroxy-5α-ergost-22E-en-7-one ( 2 ), (3α,5α),(8β,11β)-diepidioxy-ergost-22E-en-12-one ( 3 ), were isolated and characterized from dried fruit bodies of Trametes orientalis. Their structures were elucidated according to spectral methods.     

5α-24-Norcholestan-3β-ol and (24Z)-Stigmasta-5,7,24(28)-trien-3β-ol,Two New Marine Sterols from the Pacific Sponges Terpios zeteki and Dysidea herbacea

The steroidal components of 2 marine sponges, Terpios zeteki (from Hawaii) and Dysidea herbacea (from Australia) were fractionated through a combination of chromatographic methods, including reversed phase HPLC., and were analyzed by a combination of physical methods, including high resolution GC.-MS. and 360 MHz ¹H-NMR. T. zeteki contains 6 conventional 5α-stanols which comprise 91% of the sterol mixture, and traces (0.5%) of a new C₂₆ sterol, 5α-24-norcholestan-3β-ol. Minor amounts of conventional Δ⁵-sterols (6.5%) and of a single Δ⁴-3-ketosteroid (1.5%) were also present. In contrast, the Australian sponge (D. herbacea) contains 3 Δ^5,7-sterols which comprise 1.5% of the sterol mixture, and one new C₂₉ sterol, (24 Z)-stigmasta-5,7,24(28)-trien-3β-ol, as the major component (75%). In addition, minor amounts of conventional 5α-stanols (0.5%), Δ⁵-sterols (5%) and 5α-Δ⁷-sterols (18%) were present in this complex sterol mixture. The possible dietary or endosymbiotic origins of these sterols are discussed.