Studies towards the synthesis of polyoxygenated steroids. Reaction of 7,9(11)-diene steroids with RuO4.☆

Abstract In order to find an entry to C-ring oxygenated steroids, the reaction of ruthenium tetroxide with some Δ 7,9(11) -sterols has been explored. The reaction has been performed both at −70°C and room temperature using an equimolecular amount of the oxidant and acetone-water as solvent system in the absence of a cooxidant. The change in the temperature conditions moderately affect the yields of the reaction products. When 3β,6α- and 3β,6β-diacetoxy-Δ 7,9(11) -sterols were used the diene system was predominantly attacked at the 9(11)-double bond from the α-face of the molecule giving Δ 7 -9α-hydroxy-11-keto- and Δ 7 -9α-11α-dihydroxy-sterols. RuO 4 oxidation of cholesta-7,9(11)-dien-3β-yl acetate, yielded, in addition to the above oxidation products, minor amounts of three related C-7,C-11 oxigenated 8α,9α-epoxysterols, arising from the oxidation of both double bonds of the diene system. These results, that in part parallel those we recently found on RuO 4 oxidation of trisubstituted [Δ 4 , Δ 5 and Δ 7 ] steroidal alkenes, shed further light on the reactivity of this oxidizing agent which, neverthless, seems far from being completely understood. In addition, our procedure furnishes a reliable route to Δ 7 -9α,11β-dihydroxysterols via LiAlH 4 reduction of the 11-keto group.

[1]  A. D. Kagarlitskii,et al.  The oxidation of organic compounds , 1970 .

[2]  S. Chandrasekaran,et al.  Heterogeneous permanganate oxidations: an improved procedure for the direct conversion of olefins to .alpha.-diketones/.alpha.-hydroxy ketones , 1989 .

[3]  S. Popov,et al.  Two New Polyhydroxylated Sterols from the Sponge Dysidea fragilis , 1992 .

[4]  P. Rylander,et al.  Use of Ruthenium Tetroxide as a Multi-purpose Oxidant , 1958 .

[5]  Y. Kashman,et al.  NEW POLYHYDROXY STEROLS, DYSIDAMIDES, AND A DIDEOXYHEXOSE FROM THE SPONGE DYSIDEA HERBACEA , 1991 .

[6]  Donald G. Lee.  Phase Transfer Assisted Permanganate Oxidations , 1982 .

[7]  V. Martín,et al.  A greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compounds , 2002 .

[8]  R. Beyler,et al.  Approaches to the Total Synthesis of Adrenal Steroids.1 V. 4b-Methyl-7- ethylenedioxy-1,2,3,4,4aα,4b,5,6,7,8,10,10a β-dodecahydrophenanthrene-4 β-ol-1-one and Related Tricyclic Derivatives , 1953 .

[9]  M. Sprecher,et al.  The synthesis of 10-hydroxy-10α-testosterone , 1964 .

[10]  W. H. Elliott,et al.  Improved Aldehyde Synthesis: Preparation of 3α, 7α, 12α-Triacetoxy-5β-Cholan-23-al with Ruthenium Tetroxide in Neutral Medium , 1973 .

[11]  Vincenzo Piccialli,et al.  Two new 9,11-secosterols from the marine sponge Spongia officinalis. Synthesis of 9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7-en-9-one , 1992, Steroids.

[12]  Donald G. Lee,et al.  Oxidation of hydrocarbons. V. Oxidation of naphthalenes by ruthenium tetroxide , 1974 .

[13]  E. Caspi,et al.  Steroids containing ring A aromatic. XIV. Ruthenium tetroxide oxidation of aromatic steroids , 1969 .

[14]  Vincenzo Piccialli,et al.  Studies towards the synthesis of polyoxygenated steroids. Reaction of some tri- and tetra-substituted monoene steroids with RuO4☆ , 1993 .

[15]  D. Doddrell,et al.  Pyridine-induced solvent shifts in the nuclear magnetic resonance spectra of hydroxylic compounds , 1968 .

[16]  R. West,et al.  Isolation and identification of eight new polyhydroxylated sterols from the sponge Dysidea etheria , 1988 .

[17]  L. Fieser,et al.  Permanganate Oxidation of Ergosterol , 1953 .

[18]  V. Martín,et al.  Efficient oxidation of phenyl groups to carboxylic acids with ruthenium tetraoxide. A simple synthesis of (R-γ-caprolactone, the pheromone of Trogoderma granarium). , 1990 .

[19]  P. Laszlo.  Solid-supported Oxidants , 1991 .

[20]  R. West,et al.  Three new polyhydroxylated sterols with the 5.beta.-configuration from the sponge Dysidea etheria , 1989 .

[21]  K. Kondo,et al.  A Facile Procedure for Oxidative Cleavage of Enolic Olefins to the Carbonyl Compounds with Ruthenium Tetraoxide (RuO4). , 1986 .

[22]  V. Piccialli,et al.  Structure elucidation and synthesis of 3β, 6α-dihydroxy-9-oxo-9, 11-seco-5α-cholest-7-en-al, a novel 9,11-secosterol from the sponge Spongia officinalis , 1991 .

[23]  E. Caspi,et al.  Oxidation of steroidal ketones. VII. Cleavage of steroidal conjugated ketones with ruthenium tetroxide , 1969 .

[24]  M. Tishler,et al.  The Preparation of Δ7,9(11)-allo-Steroids by the Action of Mercuric Acetate on Δ7-allo-Steroids , 1953 .