Synthesis and biological activity of 1.ALPHA.-fluoro-25-hydroxyvitamin D3.

Abstract

trans Diaxial opening with potassium hydrogen difluoride of the 1β, 2β-epoxy-3β-ol derived from cholenic acid gave the 1α-fluoro-2β, 3β-diol derivative. Construction of the 25-hydroxy cholesterol side chain and deoxygenation of the 2β-hydroxy group afforded 1α-fluoro-3β, 25-dihydroxycholest-5-ene, which was transformed into 1α-fluoro-25-hydroxyvitamin D3. A single dose of 1.3μg of 1α-fluoro-25-hydroxyvitamin D3 produced neither an intestinal calcium transport response nor a bone calcium mobilization response in vitamin D-deficient rats. In the same rats, 50ng of 25-hydroxyvitamin D3 produced a marked response. In contrast, 1α-fluoro-25-hydroxyvitamin D3 was 30 times more active than 25-hydroxyvitamin D3 in binding to the chick intestinal receptor for 1α, 25-dihydroxyvitamin D3. Addition of 1α-fluoro-25-hydroxyvitamin D3 to human promylocytic leukemia cells resulted in strong phagocytic activity.