A Stereospecific Synthesis of 24(<i>S</i>)-Hydroxyvitamin D₂, a Prodrug for 1α,24(<i>S</i>)-Dihydroxyvitamin D₂

Abstract

This contribution describes the first stereospecific synthesis of 24( S )-hydroxyvitamin D 2 ( 1 ), a metabolite of vitamin D 2 . This metabolite acts as a prodrug for 1α,24( S )-dihydroxyvitamin D 2 ( 2 ), which is under development for treatment of various diseases characterized by cellular hyperproliferation. The key step of the synthesis involves the Wittig−Horner olefination of ( S )-2,3-dimethyl-2-triethysilyloxybutyraldehyde ( 17 ) and a vitamin D 2 phosphine oxide derivative ( 22 ). The synthesis of the requisite aldehyde started with the commercially available l -(+)-valine and was completed in seven steps. The vitamin D 2 phosphine oxide derivative was synthesized in seven steps starting from vitamin D 2 .