Differential behavior of (25 R)-5,6-epoxyspirostan-22α- O-3β-ol and (25 R)-5,6-epoxyspirostan-22α- O-3β,4β-diol toward Dowex

Abstract

The acid-catalyzed hydrolytic cleavage of the 5,6-epoxyspirostane derivatives by the cation exchange resin Dowex 50W X8 has been exploited with the goal of developing synthetic protocols toward 3,4,5,6-polyhydroxyspirostane analogs that can serve as intermediates to potential biologically active compounds. Whereas the diastereomers (25 R)-5α,6α-epoxyspirostan-22α- O-3β-ol and and (25 R)-5β,6β-epoxyspirostan-22α- O-3β-ol yield two products, (25 R)-6β- methoxyspirostan-22α- O-3β,5α-diol and (25 R)-spirostan-22α- O-3β,5α,6β-triol on Dowex treatment in water-methanol, the α- and β-diastereomers of the 5,6-epoxy derivative of 3β,4β-diol provide a single product, (25 R)-3β,6β-dihydroxy-5α-spirostan-4-one, in good yields. The structures of these products have been confirmed using 1H NMR, 13C NMR, and 1H- 1H J-correlated spectroscopies. Multifunctional product formation suggests tremendous utility of Dowex in steroid synthesis. The product formation has been rationalized on the basis of differential conformational constraints of the A/B rings of the different epoxides in directing the reaction course. The reaction shows an interesting example of stereoelectronic effect of a single hydroxy group in discriminating solvent participation.