Synthetic studies on active forms of vitamin D and their analogues

Abstract

Active forms of vitamin D derivatives in addition to the traditional role in calcium homeostasis play an role in cellar differentiation. The hydroxylation at C-1α-position of vitamin D molecule is essential to elicit the physiological activities. We have developed a new method for the selective 1α-hydroxylation process in the steroidal molecule via enol esterification rearrangement of the 1, 4, 6-trien-3-ones. This review deals with the syntheses of important intermediates for the preparation of active forms of vitamin D and their conversion into the active forms of vitamin D. The steroidal synthon, 1α, 3β-dihydroxy-5, 7-choladiene derivatives obtained from ergosterol or stigmasterol was converted into the various active forms of vitamin D compounds by coupling with phenylsulfonyl derivatives. Similar treatment of pregnenolone afforded (20 R and 20 S)-1α, 3β-dihydroxy-5, 7-pregnadiene derivatives. According to the procedure described here, 1α-hydroxy and 1 a, 25-dihydroxyvitamin D2, D3, D4, and D7, 24-epi-1α, 25-dihydroxyvitamin D2, 1α, 24dihydroxyvitamin D3, 24, 24-dihomo-1α, 25-dihydroxyvitamin D3 and 1α, 25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3 were synthesized. © 1995, The Society of Synthetic Organic Chemistry, Japan. All rights reserved.