Synthesis of 2α- and 2β-substituted-14-epi-previtamin D3 and their genomic activity

Abstract 2α- and 2β-Substituted analogs of 14- epi -previtamin D 3 were synthesized and isolated after thermal isomerization of 14- epi -vitamin D 3 triene at 80 °C. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were tested, and the 2α-methyl-substituted analog was found to have greater genomic activity than 14- epi -previtamin D 3 . We found that modification at the C2 position of the seco -steroidal skeleton afforded interesting effects for biological genomic activity for the previtamin D form as well as the natural vitamin D form.