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

Abstract

To investigate the biological profile of the previtamin form of vitamin D, we have synthesized new analogues of 19-nor-1α,25-dihydroxyprevitamin D3 bearing a 2-hydroxyethylidene moiety at the A-ring. The target compounds were prepared by convergent synthesis employing the 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 starting material for the synthesis of the A-ring precursors. The binding affinity to Vitamin D Receptor (VDR) and Vitamin D Binding Protein (DBP), and MCF-7 cell antiproliferative activity have been evaluated.