Synthesis and biological activity of (22 E, 25 R)- and (22 E,25 S)-22-dehydro-1α, 25-dihydroxy-26-methylvitamin D 3

Abstract

Both 25-epimers of (22 E)-22-dehydro-1α,25-dihydroxy-26-methylvitamin D 3 [22-dehydro-26-methyl-1, 25-(OH) 2D 3] were synthesized. The biological activity of these compounds was tested in binding affinity to chick intestinal receptor protein of 1α,25-dihydroxy-vitamin D 3 [1,25-(OH) 2D 3] and in stimulating for intestinal calcium transport and bone calcium mobilization with vitamin D-deficient rats. The relative potency of (25 R)- and (25 S)-22-dehydro-26-homo-1,25-(OH) 2D 3 and 1,25-(OH) 2D 3 in competing for the intestinal cytosolic binding was 1.7:1.5:1. A similar order of activity was observed on intestinal calcium transport and bone calcium mobilization. In the ability for stimulation of intestinal calcium transport, (25 R)- and (25 S)-22-dehydro-26-methyl-1,25-(OH) 2D 3 were about 3.6 and 2.1 times as active as 1,25-(OH) 2D 3, respectively. In bone calcium mobilization tests, (25 R)- and (25 S)-22-dehydro-26-methyl-1,25-(OH) 2D 3 were estimated to be 2.2 and 1.6 times as potent as 1,25-(OH) 2D 3, respectively.