A stereospecific synthesis of 24(S)-hydroxyvitamin D2, a prodrug for 1α,24(S)-dihydroxyvitamin D2

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 1alpha,24 (S)-dihydroxy vitamin 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 D2 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.