CH(3)ReO(3)-catalyzed oxidation of cholesta-5,7-dien-3beta-yl acetate with the urea-hydrogen peroxide adduct under various conditions. Synthesis of the natural epoxy sterol 9alpha,11alpha-epoxy-5alpha-cholest-7-en-3beta,5,6beta-triol.
This article describes the oxidation of cholesta-5,7-dien-3beta-yl acetate (4) with the urea-hydrogen peroxide adduct (UHP) using methyltrioxorhenium (MTO) as catalyst, under various conditions. Specifically, the effects of using different solvents (CHCl(3) and ethers) and additives (EtOH and pyridine) on the course of the MTO-catalyzed oxidation of 4 were investigated. Some new steroids (6, 9, 10 and 11), obtained from this oxidation, were isolated and characterized on the basis of chemical evidence and interpretation of spectroscopic data including H-H COSY and HMBC experiments. The optimal solvent for the oxidation of 4 with MTO/UHP oxidizing system was diethyl ether. In this solvent the reaction is clean and gave as the main product 5,6beta-dihydroxy-5alpha-cholest-7-en-3beta-yl acetate (8, 65% yield), obtained with a more simple procedure and with a higher yield than that reported in literature. Sterol 8 is a key intermediate compound in the synthesis of many steroids of marine origin, biologically active, oxygenated at the B/C rings. In fact, starting from diol 8, we performed the synthesis of the natural cytotoxic epoxy sterol 9alpha,11alpha-epoxy-5alpha-cholest-7-en-3beta,5,6beta-triol (15, 21% yield) with an improvement in yield and number of steps over a synthesis of the same natural product previously reported. When the oxidation of 4 with the MTO/UHP system in diethyl ether was performed in the presence of pyridine as ligand, the unsaturated epoxide 5,6alpha-epoxy-5alpha-cholest-7-en-3beta-yl acetate (10, 90% yield) was obtained after only 5 min in good yield. In fact, pyridine, besides having beneficial effect on the reaction rate, shuts down the ring opening reactions, as reported in literature.
Musumeci
Domenica
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Dipartimento di Chimica Organica e Biochimica, Università degli Studi di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, Via Cintia, Italy.
Sica
Donato
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D002384:Catalysis; D002774:Cholestadienes / Q000138:chemical synthesis* / Q000737:chemistry; D002784:Cholesterol / Q000138:chemical synthesis* / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013261:Sterols / Q000138:chemical synthesis* / Q000737:chemistry; D014508:Urea / Q000737:chemistry
C467542:9,11-epoxy-5-cholest-7-en-3,5,6-triol; D002774:Cholestadienes; D009942:Organometallic Compounds; D013261:Sterols; C467541:cholesta-5,7-dien-3-yl acetate; C411866:methyltrioxorhenium VII; D014508:Urea; D002784:Cholesterol; D006861:Hydrogen Peroxide