Introduction of Fluorine Atoms to Vitamin D3 Side-chain and Synthesis of 24,24-Difluoro-25-hydroxyvitamin D3

Abstract During our ongoing studies of vitamin D, we focused on the vitamin D3 side-chain 24-position, which is the major metabolic site of human CYP24A1. In order to inhibit the metabolism of vitamin D3, 24,24-difluorovitamin D3　analogues are important candidates. In this paper, we report the practical introduction of the difluoro-unit to the 24-position to synthesize 24,24-difluoro-CD ring (1) and 24,24-difluoro-25-hydroxyvitamin D3 (2).