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

Novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D(3) analogues with 2alpha-alkyl and 2alpha-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 2alpha-hydroxypropyl group best fits the cavity of the LBD, and the binding activity is three times higher than that for the natural hormone.