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

2α- and 2β-Substituted analogs of 14-epi-previtamin D3 were synthesized and isolated after thermal isomerization of 14-epi-vitamin D3 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 D3. 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.

2-Substituted analogs of 14-epi-1,25-dihydroxyprevitamin D3 were synthesized and their preliminary biological activity was evaluated.