STUDIES OF VITAMIN-D (CALCIFEROL) AND ITS ANALOGS .41. 18-SUBSTITUTED DERIVATIVES OF VITAMIN-D - 18-ACETOXY-1-ALPHA,25-DIHYDROXYVITAMIN-D3 AND RELATED ANALOGS

The bridged ether 6, produced via light-induced lead tetraacetate oxidation of Grundmann's alcohol 5, was transformed in three to four steps to the CD-ring ketones 9b and 10 which were then transformed via Homer-Wittig coupling to the 18-acetoxy analogues of vitamin D3, 25-hydroxyvitamin D3, 1-alpha,25-dihydroxyvitamin D3, and 1-alpha-hydroxyvitamin D3 (4a-d, respectively). The biological evaluation of 4a-d in terms of their ability to elicit intestinal calcium absorption and bone calcium mobilization in vivo in the chick is reported. These vitamin D analogues, the first in this steroid series modified at the C-18 position, are nearly devoid of activity. In vitro data for 4a-d in terms of their ability to bind to the chick intestinal receptor as compared to the natural hormone 1-alpha,25-dihydroxyvitamin D3, parallels the in vivo data.