Synthesis and biological activity of previtamin D 3 analogues with A-ring modifications

Abstract

Synthesis of two novel 6- s- cis analogues of 1α,25-dihydroxyvitamin D 3 are described using shikimic acid and its 4- epi isomer as versatile chiral starting materials. These derivatives contain a 2β-(3′-hydroxypropoxy) moiety or a 2β,3β-epoxy group into 1α,25-(OH) 2-19- nor-pre-D 3. The synthesized analogues were found to be not suitable for binding to the vitamin D receptor and showed weak binding affinity toward the vitamin D-binding protein. The new derivatives failed to inhibit cell proliferation.