Efficient and Versatile Synthesis of Novel 2α-Substituted 1α,25-Dihydroxyvitamin D3 Analogues and Their Docking to Vitamin D Receptors

Abstract
Novel 2α-substituted 1α,25-dihydroxyvitamin D3 analogues with 2α-alkyl and 2α-hydroxyalkyl groups were systematically synthesized from d-xylose. Their conformation on binding to the ligand binding domain (LBD) of the vitamin D receptor was analyzed. It has been found that the 2α-hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.