DIFFERENTIAL BEHAVIOR OF (25R)-5,6-EPOXYSPIROSTAN-22-ALPHA-O-3-BETA-OL AND )-5,6-EPOXYSPIROSTAN-22-ALPHA-O-3-BETA,4-BETA-DIOL TOWARD DOWEX

The acid-catalyzed hydrolytic cleavage of the 5,6-epoxyspirostane deri vatives by the cation exchange resin Dowel 50W X8 has been exploited w ith the goal of developing synthetic protocols toward 3,4,5,6-polyhydr oxyspirostane analogs that can serve as intermediates to potential bio logically active compounds. Whereas the diastereomers (25R)-5 alpha,6 alpha-epoxyspirostan-22 alpha-O-3 beta-ol and (25R)-5 beta,6 beta-epox yspirostan-22 alpha-O-3 beta-ol yield two products, (25R)-6 beta-metho xyspirostan-22 alpha-O-3 beta,5 alpha-diol and (25R)-spirostan-22 alph a-O-3 beta,5 alpha,6 beta-triol on Dowex treatment in water-methanol, the alpha- and beta-diastereomers of the 5,6-epoxy derivative of 3 bet a,4 beta-diol provide a single product, (25R)-3 beta,6 beta-dihydroxy- 5 alpha-spirostan-4-one, in good yields. The structures of these produ cts have been confirmed using H-1 NMR, C-13 NMR, and H-1-H-1 J-correla ted spectroscopies. Multifunctional product formation suggests tremend ous utility of Dowex in steroid synthesis. The product formation has b een rationalized on the basis of differential conformational constrain ts of the A/B rings of the different epoxides in directing the reactio n course. The reaction shows an interesting example of stereoelectroni c stereoelectronic effect of a single hydroxy group in discriminating solvent participation.