A New and Convenient Synthesis of 1α,25-Dihydroxyvitamin D2 and Its 24R-Epimer

1α, 25-Dihydroxyvitamin D2 (1a) was synthesized by irradiation and subsequent thermal isomerization of (22E)-5,7,22-ergostatriene-1α,3β,25-triol (16a). The triol 16a was obtained via 22-oxo-5α,8α-(4-phenyl-3,5-dioxo-1,2,4-triazolidine-1,2-diyl)-23,24-dinor-6-cholene-1α,3β-diyl diacetate (12) starting from (22E)-5,7,22-ergostatriene-1α,3β-diyl diacetate (10), a precursor of 1α-hydroxyvitamin D2. Introduction of the new side chain with the desired stereochemistry was carried out selectively by the reductive elimination of the β-hydroxy sulfone derived from the C-22 aldehyde (12) and an optically active sulfone, prepared via (S)-2,3-dimethyl-1,3-butanediol from methyl (S)-3-hydroxy-2-methylpropionate. Similarly a C-24 epimer of 1a was synthesized.

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