Transformation of (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one into (20S)-20-(p-toluene-sulfonyloxymethyl)pregna-1,5-dien-3β-ol and -3α-ol: Intermediates of vitamin D derivatives

Article abstract of DOI:10.1002/prac.19963380145

Efficient three-step approaches to the two 3-epimeric 22-tosylated 1,5-diene-3,22-diols 6 and 7 starting with (20S)-20-(hydroxymethyl)pregna-1,4-dien-3-one (1) were developed and optimized. Isomerization of 1 to the 1,5-dien-3-one 3 and subsequent tosylation furnished the deconjugated 3-ketone 4. The 3β-alcohol 6 was available from 4 by means of in situ generated calcium borohydride. Treatment of 4 with lithium trisiamylborohydride (LS-Selectride) afforded the highest yield of the hitherto unknown 3α-epimer 7. Following the optimized synthesis, 6 and 7 were obtained from 1 in 60 % and 50 % overall yield, respectively.