Synthesis and biological activity of (22E,25R)- and (22,25S)-22-dehydro- 1 alpha,25-dihydroxy-26-methylvitamin D3.
Both 25-epimers of (22E)-22-dehydro-1 alpha,25-dihydroxy-26-methylvitamin D3 [22-dehydro-26-methyl-1,25-(OH)2D3] were synthesized. The biological activity of these compounds was tested in binding affinity to chick intestinal receptor protein of 1 alpha,25-dihydroxy-vitamin D3 [1,25-(OH)2D3] and in stimulating for intestinal calcium transport and bone calcium mobilization with vitamin D-deficient rats. The relative potency of (25R)- and (25S)-22-dehydro-26-homo-1,25-(OH)2D3 and 1,25-(OH)2D3 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, (25R)- and (25S)-22-dehydro-26-methyl-1,25-(OH)2D3 were about 3.6 and 2.1 times as active as 1,25-(OH)2D3, respectively. In bone calcium mobilization tests, (25R)- and (25S)-22-dehydro-26-methyl-1,25-(OH)2D3 were estimated to be 2.2 and 1.6 times as potent as 1,25-(OH)2D3, respectively.
Hara
N
N
Department of Chemistry, Tokyo Institute of Technology, Meguro-ku, Japan.
Eguchi
T
T
Ikekawa
N
N
Ishizuka
S
S
Sato
J
J
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D006900:Hydroxylation; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; C064781:25-dehydro-1,25-dihydroxy-26-methylvitamin D3; D002117:Calcitriol; D002118:Calcium