REDUCTION OF 17-ALPHA-HYDROXY-20-KETO STEROIDS - CONVENIENT SYNTHESIS OF (E)-3-BETA-HYDROXY-5,17(20)-PREGNADIENE 3-PIVALOATE AND (Z)-3-BETA,16-ALPHA-DIHYDROXY-5,17(20)-PREGNADIENE 3-PIVALOATE

Reduction of the 20-keto group of both 17a-hydroxy- and 16a-alkoxy-17a-hydroxy steroids has been examined with various hydride reagents in a number of different solvent systems. For each of these steroids, specific conditions have been established to cleanly reduce to (20R)-17a,20-a-diols. These conditions have been applied to the synthesis of (E)-3β-hydroxy-5,17(2O)-pregnadiene 3-pivaloate (5) and (Z)-3β,6a-dihydroxy-5,17(20)-pregnadiene 3-pivaloate (6) from commercially available 3&17a-dihydroxy-5-pregnen-20-one (7a) and 3β-hydroxy-5,16-pregnadien-20-one (11a), respectively. The pivaloate derivative of 7a was reduced with L-Selectride in THF to provide, after mild acid treatment and oxidative workup, (20R)-17a,20-diol 9 as a single stereoisomer in 86% yield. Subsequent syn-dideoxygenation of its thionocarbonate derivative with triethyl phosphite afforded pure (E)-ethylidene 5 in 56% overall yield from 7a. [2-(Trimethylsilyl)ethoxy]methyl (SEM) ether derivative of the 16a-hydroxy group of 3β,16a,17a-trihydroxy-5-pregnen-20-one 3-pivaloate (13b), obtained in two steps from 11a, was reduced with (n-Bu)4NBH4in THF to provide, after mild acid treatment of the quenched solution, (20R)-17a,20-diol 14b as a single stereoisomer in 90% yield. Similar dideoxygenation of the diol followed by deprotection of the SEM group with CsF gave 16a-hydroxylated (Z)-17-ethylidene 6 in 48% overall yield from 11a. In addition, results on stereoselective syn-deoxygenation of (20S)-17a,20-epoxides are also discussed. © 1990, American Chemical Society. All rights reserved.