New vitamin D3 derivatives with unexpected antiproliferative activity: 1-(hydroxymethyl)-25-hydroxyvitamin D3 homologs

Publisher Website
Google Scholar
Abstract
Surprisingly, both of the synthetic 1-(hydroxymethyl)-25-hydroxyvitamin D3 diastereomers (-)-2 and (+)-3 retained the antiproliferative activity of natural calcitriol in murine keratinocytes. Preliminary studies indicated, however, that both of these synthetic diastereomers were less than 0.1% as effective as calcitriol for binding to the 1,25-(OH)2-D3 receptor and that they were less than 0.1% as potent as calcitriol for calbindin-D28K induction in organ-cultured embryonic chick duodenum. 1-(Hydroxymethyl)-25-hydroxyvitamin D3 homologs (-)-2 and (+)-3 were synthesized in a convergent manner by combining enantiomerically pure C,D-ring ketone 12 with highly enantiomerically enriched A-ring phosphine oxides (-)-11a and (+)-11b. These A-ring chirons were prepared starting from thermal [2 + 4] cycloaddition of 3-bromo-2-pyrone and acrolein.

This publication has 0 references indexed in Scilit: