ABSTRACT
Readily available vanadyl acetylacetonate was found to oxidize the allylic sites of Δ(5) steroidal alcohols without protection of hydroxyl groups. Cholesterol, dehydroepiandrosterone, cholesterol benzoate, cholesterol acetate, pregnenolone, and 5-pregnen-3,20-diene were oxidized to 7-keto products using vanadyl acetylacetonate in one pot reactions at room temperature in the presence of oxygen and water.
Subject(s)
Alkenes/chemistry , Hydroxybutyrates/chemistry , Pentanones/chemistry , Steroids/chemistry , tert-Butylhydroperoxide/chemistry , Benzene/chemistry , Oxidation-ReductionABSTRACT
An allylic oxidation method for Delta(5)-steroids using TBHP as oxidant with a 2-quinoxalinol salen Cu(II) complex as catalyst is reported. A variety of Delta(5)-steroidal substrates are selectively oxidized to the corresponding enones. Excellent yields are achieved (up to 99% under optimized conditions) while significantly reducing reaction times required as compared to other current methods.
Subject(s)
Allyl Compounds/chemical synthesis , Copper/chemistry , Organometallic Compounds/chemistry , Steroids/chemical synthesis , tert-Butylhydroperoxide/chemistry , Allyl Compounds/chemistry , Catalysis , Magnetic Resonance Spectroscopy , Models, Chemical , Molecular Structure , Oxidation-Reduction , Stereoisomerism , Steroids/chemistrySubject(s)
Congresses as Topic , Sterols , Animals , Humans , Portraits as Topic , Research , WashingtonABSTRACT
Oxygenated derivates of cholesterol and lanosterol, known as oxysterols, have consistently displayed significant activity as inhibitors of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, a key regulatory enzyme in sterol biosynthesis. We have developed the chemical syntheses of ring C oxysterols for evaluation as inhibitors of sterol biosynthesis. A key intermediate in the chemical synthesis was 3beta-benzoyloxy-9alpha, 1alpha-epoxy-5alpha-cholest-7-ene (1), whose structure was confirmed by X-ray crystallographic analysis and is presented herein.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Hydroxymethylglutaryl CoA Reductases/metabolism , Enzyme Inhibitors/pharmacology , Hydroxymethylglutaryl CoA Reductases/drug effects , Sterols/chemical synthesis , Sterols/chemistryABSTRACT
Steroids bearing ketone functionality at carbon-7 are found commonly in nature, and the most prevalent of these are the 7-keto-delta5-sterols. These substances have diverse biological properties and are present in biological samples and food products. For the purpose of studying this class of oxysterols, many chemical methods, involving the chemical oxidation of delta5-sterols to the corresponding 7-keto-delta5-sterol derivatives have been developed to produce these compounds. We have undertaken a review and evaluation of chemical methods for the synthesis of these compounds and have endeavored to enhance one of these procedures to yield products for chemical and biological investigations.
Subject(s)
Sterols/chemical synthesis , Animals , Sterols/chemistryABSTRACT
This article reviews the utility of dioxiranes in the oxidation of 3beta-substituted delta5-sterols. Dioxiranes are the smallest cyclic peroxides that contain a carbon atom. They can be generated in situ from Oxone (2KHSO5.KHSO4.K2SO4) and a ketone. Dioxiranes are versatile oxidizing agents. The most common reaction of dioxiranes is epoxidation, with nearly 1:1 ratios of alpha/beta isomer products in all cases. delta5-Steroids with different side chains were epoxidized by dioxiranes generated in situ from several commercially available ketones. Although ketones function as catalyst, they were used in about an equivalent amount or large excess to accelerate the reaction.
Subject(s)
Epoxy Compounds/chemistry , Steroids/chemistry , Animals , Ketones/chemistry , Oxidation-ReductionABSTRACT
Pneumocystis causes a type of pneumonia in immunodeficient mammals, such as AIDS patients. Mammals cannot alkylate the C-24 position of the sterol side chain, nor can they desaturate C-22. Thus, the reactions leading to these sterol modifications are particularly attractive targets for the development of drugs against fungal and protozoan pathogens that make them. In the present study, the definitive structures of 43 sterol molecular species in rat-derived Pneumocystis carinii were elucidated by nuclear magnetic resonance spectroscopy. Ergosterol, Delta(5,7) sterols, trienes, and tetraenes were not among them. Most (32 of the 43) were 24-alkylsterols, products of S-adenosyl-L-methionine:C-24 sterol methyl transferase (SAM:SMT) enzyme activity. Their abundance is consistent with the suggestion that SAM:SMT is highly active in this organism and that the enzyme is an excellent anti-Pneumocystis drug target. In contrast, the comprehensive analysis strongly suggest that P. carinii does not form Delta(22) sterols, thus C-22 desaturation does not appear to be a drug target in this pathogen. The lanosterol derivatives, 24-methylenelanost-8-en-3 beta-ol and (Z)-24-ethylidenelanost-8-en-3 beta-ol (pneumocysterol), previously identified in human-derived Pneumocystis jiroveci, were also detected among the sterols of the rat-derived P. carinii organisms.
Subject(s)
Pneumocystis/chemistry , Sterols/chemistry , Sterols/isolation & purification , Acquired Immunodeficiency Syndrome/parasitology , Animals , Chromatography, Gas , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Molecular Structure , RatsABSTRACT
Steroidal dienones represent a significant class of compounds that are useful intermediates in the further functionalization of the steroid nucleus. Their chemical synthesis can be problematic owing to the lack of a simplified method of preparation and the occurrence of impurities that can be difficult to remove. We have endeavored to develop new methods of chemical synthesis of cholest-4,6-dien-3-one that would yield a product of high purity.
