26,27-Dihomo-1 alpha-hydroxy- and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 analogs that differ markedly in biological activity in vivo.
26,27-Dihomo-1 alpha-hydroxyvitamin D2, 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2, and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 have been synthesized. In contrast to 1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha-hydroxyvitamin D2, 26,27-dihomo-1 alpha-hydroxyvitamin D2 (1) and the 24-epi analog (2) have no activity in intestinal calcium transport, bone calcium mobilization, or skeleton mineralization. On the other hand, 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D2 is equal to 1,25-dihydroxyvitamin D3 in biological activity. Vitamin D 25-hydroxylase readily converts 1 alpha-hydroxyvitamin D2 to 1,25-dihydroxyvitamin D2. In contrast, the same preparations fail to hydroxylate 26,27-dihomo-1 alpha-hydroxyvitamin D2 and 26,27-dihomo-24-epi-1 alpha-hydroxyvitamin D2 on carbon 25. Thus, homologation of carbons 26 and 27 of the vitamin D compound likely sterically hinders vitamin D 25-hydroxylase.
Perlman
K L
KL
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
Prahl
J M
JM
Smith
C
C
Kutner
A
A
DeLuca
H F
HF
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004872:Ergocalciferols / Q000737:chemistry / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012279:Rickets / Q000188:drug therapy; D013329:Structure-Activity Relationship
D004872:Ergocalciferols; D002118:Calcium