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Inhibitors of sterol synthesis. An improved chemical synthesis of 26-oxygenated delta 8(14)-15-ketosterols having the 25R configuration. 1994

A U Siddiqui, and W K Wilson, and G J Schroepfer
Department of Biochemistry, Rice University, Houston, Texas 77251-1892.

(25R)-3 beta,26-Dihydroxy-5 alpha-cholest-8(14)-en-15-one (I) was synthesized in four steps from (25R)-3 beta,26-diacetoxycholesta-5,7-diene (III) in 30% overall yield. Isomerization of III with HCl in chloroform-dichloromethane at -60 degrees C gave (25R)-3 beta,26-diacetoxy-5 alpha-cholesta-7,14-diene together with the 5 alpha-delta 8,14 and 5 beta-delta 8,14 isomers in a 5:1:1 ratio. Epoxidation of the crude diene mixture with m-chloroperbenzoic acid, followed by hydrolysis in acetone containing concentrated HClO4 (0.1%) gave (25R)-3 beta,26-diacetoxy-5 alpha-cholest-8(14)-en-15-one (VIII), accompanied by numerous minor byproducts, including the 5 alpha,14 beta-delta 7, 5 alpha, 14 beta-delta 8 and 5 beta,14 beta-delta 8 isomers of VIII. All four 15-ketosterol esters were isolated by chromatography and fully characterized by mass spectrometry and 1H and 13C nuclear magnetic resonance. Treatment of VIII with potassium carbonate in degassed methanol gave I.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013261 Sterols Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987) Sterol

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