26,27-DIHOMO-1-ALPHA-HYDROXY-VITAMIN-D-2 AND 6,27-DIHOMO-24-EPI-1-ALPHA,25-DIHYDROXYVITAMIN-D-2 ANALOGS THAT DIFFER MARKEDLY IN BIOLOGICAL-ACTIVITY IN-VIVO

26,27-Dihomo-1 alpha-hydroxyvitamin D-2, 26,27-dihomo-24-epi-1 alpha-h ydroxyvitamin D-2, and 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D-2 have been synthesized. In contrast to 1 alpha-hydroxyvitamin D-2 and 24-epi-1 alpha-hydroxyvitamin D-2, 26,27-dihomo-1 alpha-hydroxyvit amin D-2 (1) and the 24-epi analog (2) have no activity in intestinal calcium transport, bone calcium mobilization, or skeleton mineralizati on. On the other hand, 26,27-dihomo-24-epi-1 alpha,25-dihydroxyvitamin D-2 is equal to 1,25-dihydroxyvitamin D-3 in biological activity. Vit amin D 25-hydroxylase readily converts 1 alpha-hydroxyvitamin D-2 to 1 ,25-dihydroxyvitamin D-2. In contrast, the same preparations fail to h ydroxylate 26,27-dihomo-1 alpha-hydroxyvitamin D-2 and 26,27-dihomo-24 -epi-1 alpha-hydroxyvitamin D-2 on carbon 25. Thus, homologation of ca rbons 26 and 27 of the vitamin D compound likely sterically hinders vi tamin D 25-hydroxylase.