Stereoselectivity of directed epoxidations of 22-hydroxy-Δ²³-sterol side chains

Abstract

A series of 22-hydroxy-A''-sterols comprising (3~,5a,6~,22S)-6-methoxy-3,5-~y~l0-25,26,27-trinorcholest-23-en- 22-01 (6), (3~,5a,6~,22S,23E)-6-methoxy-3,5-cyclo-26,27-dinorcholest-23-en-22-ol (7), 3P,5a,6P,22R)-6-methoxy-23-methyl-3,5-cyclo-25,26,27-trinorcholest-23-en-22-ol(10), 3~,5a,6~,22S,23~-6-methoxy-3,5-cyclo-26,27-dinorcholest-23-en-22-01 ( l l ) , and 3~,5a,6~,22R)-6-methoxy-3,5-cyclo-26,27-dinorergost-23-en-22-ol (12) were subjected to epoxidation with /)I-chloroperbenzoic acid and [err-butyl hydroperoxide in the presence of either vanadyl acetoacetonate or molybdenum hexacarbonyl, and the rhreo:eryrhro ratios of the products were determined. The results are of relevance for the synthesis of sterols with oxygenated side chains, such as brassinolide (I). The oxidations of 6 and 7 were er.y~hro selective with all three oxidants, especially with the vanadium-catalyzed system. Peracid oxidation of the 22-[err-butyldimethylsilyl ether (8) and 22-pivaloate (9) of alcohol 7 showed similar elyrhro selectivity to that of the parent compound 7. Allylic alcohol 10 gave exclusively the eryrhro epoxide with all three oxidants, while 11 and 12 were threo-selective under all three conditions. Molecular modeling indicated that eryrhro selectivity in the vanadium-catalyzed epoxidation of 10 was consistent with a destabilizing interaction (~( 1 . 2 1 strain) between the getn-methyl and C(2 I) methyl groups in the conformation required for formation of the rhreo-isomer. The ttrreo-selective peracid oxidations of 11 and 12 were attributed to A''.~) strain between the cis-methyl groups and C(20) in the conformation required for formation of the etyrhm-epoxide. The differences in the calculated energies of conformations leading to the rhreo-and eryrhro epoxide diastereomers of substrates containing no gem or cis substituents proved too small to permit reliable prediction of diastereoselectivity.Key words: 22-hydroxy-A'3-stero~s, brassinosteroids, allylic alcohols, epoxidation, diastereoselectivity I R6sumC : On a soumis une sCrie de 22-hydroxy-Ax-st~rols, comportant les (3P,5a,6P,22S)-6-mCthoxy-3,5-cyclo-25,26,27-trinorcholkst-23-Cn-22-01(6), (3~,5a,6~,22S,23E)-6-mCthoxy-3,5-cyclo-26,27-dinorcholkst-23-en-22-ol(7), 3P,5a,6P,22R)-6-mCthoxy-23-mCthyl-3,5-cyclo-25,26,27-trinorcholCst-23-Cn-22-ol (lo), 3P,5a,6P,22S,23~-6-mCthoxy-3,5-cyclo-26,27-dinorcholkst-23-en-22-01 ( l l ) , et 3~,5a,6~,22R)-6-mCthoxy-3,5-cyclo-26,27-dinorergost-23-n-22-o (12), i une Cpoxydation par I'acide tn-chloroperbenzo'ique et l'hydroperoxyde de re,?-butyle, en prksence soit d'actoacCtonate de vanadyle soit d'hexacarbonyle de molybdkne; on a dCterminC les rapport rhrio/e'ryrhro des produits obtenus. Les rtsultats prCsentent de I'importance pour la synthkse de stCrols portant des chaines IatCrales oxygCnCes, comme le brassinolide (1). Les oxydations des composes 6 et 7 sont tryrhro-stlectives avec chacun des trois oxydants, particulikrement avec le systkme catalysC par le vanadium. Les oxydations du 22-terr-butyldimCthylsilyloxyde (8) et du 2...

Donor Properties of the Vanadyl Ion: Reactions of Vanadyl Salicylaldimine β-Ketimine and Acetylacetonato Complexes with Groups 14 and 15 Lewis Acids

“…Several vanadyl complexes show excellent antibacterial activity against Streptococcus pneumoniae , wherein the vanadium complexes inhibit substrate transport through the cell membrane . Examples of catalytic applications by vanadyl complexes relevant to the present study are the use of VO(acac) 2 as a catalyst in the stereoselective epoxidation of 2,2-hydrox-δ-sterol side chains using MCPBA or tert -butyl hydroperoxide as oxidant, giving the erythro form as the major sterol enantiomer . Polymer-bound VO(acac) 2 is a catalyst for the conversion of benzene to phenol.…”

Steroids: reactions and partial synthesis

“…201 Other synthetic studies on the construction of the sterol side chain which have been reported include the use of chlorosulfones, 202 methods for the formation of 26,27-cyclopropylsterols, 203 and the application of 22-cupriosteroids. 204 Stereoselectivity in the epoxidation 205 and hydroxylation 206 of side chain double bonds has been examined. The results have been used in the elucidation of the structure of an ecdysteroid, gerardiasterone, 93, 206 and in the preparation 207 of possible intermediates in the formation of bile acids from cholesterol.…”