Synthetic Studies of Vitamin D Analogues. XVII.Synthesis and Differentiation-Inducing Activity of 1α, 24-Dihydroxy-22-oxavitamin D₃ Analogues and Their 20(R)-Epimers

Abstract

Four vitamin D₃ analogues, 1α, 24(S)-and 1α, 24(R)-dihydroxy-22-oxavitamin D₃ (5 and 6) and their 20(R)-epimers (7 and 8) were synthesized from the 20(S)-alcohol (10). In tests of activity to induce differentiation of human myeloid leukemia cells (HL-60) to macrophages, 5 showed comparable activity to 1α, 25-dihydroxy-22-oxavitamin D₃ (OCT) (2), and the other three analogues (6, 7 and 8) were less active than OCT (2). The binding properties of these analogues to the chick embryonic intestinal 1α, 25-dihydroxyvitamin D₃ (1) receptor were evaluated. Furthermore, 20(R)-OCT (9) was synthesized and its biological properties were compared with those of OCT (2) and the 20(R)-epimers (7 and 8).