Distereoselective Approaches to trans-Hydrinadane Derivatives - Total Synthesis of 8-(Phenylsulofnyl)de-A,B-cholestane Precursor to 25-Hydroxyvitamin D_3

摘要

The total diastereoselective synthesis of the C,D rings/side chain building block for the synthesis of 1alpha, 25-dihydroxyvitamin D_3 is described. Two tandem Mukaiyama-Michael additions involving silylated ketene acetals derived from tert-butyl 6-methylhept-5-enethioate or tert-butyl 16-methylhept-6-enethioate, 2-methylcyclopent-2-en-1-one, and 1-(phenylthio) but-3-en-2-one afforded the corresponding intermediates with the complete carbon framework of the target compound. The further transformation of these key intermediates involves cyclization, oxidation with m-CPBaA, and reduction of the vinylic sulfone moiety of afford the trans-hydrindane ring system. The synthesis comprises five operations and afforded the product in ca. 30% yield. The application of 2-[(phenylthio)methyl]-2-vinyl [1,3] dioxolane and 2-(phenylsulfonylmethyl)-2-vinyl [1,3] dioxolane as Michael acceptors was also examined.