A-Ring-Modified 2-Hydroxyethylidene Previtamin D3 Analogues: Synthesis and Biological Evaluation

To investigate the biological profile of the previtamin form of vitamin D, we synthesized new analogues of 19-nor-1 alpha, 25-dihydroxyprevitamin D-3 bearing a 2-hydroxyethylidene moiety at the A-ring. The target compounds were prepared by convergent synthesis using a Sonogashira coupling between an A-ring enyne synthon and a CD-ring/side-chain vinyl triflate. We have demonstrated the versatility of shikimic acid as a starting material for the synthesis of the A-ring precursors. The binding affinity to vitamin D receptor (VDR) and human vitamin D binding protein (hDBP), and the MCF-7 cell antiproliferative activity were evaluated.