16 STEREOSELECTIVE SYNTHESES OF VITAMIN D METABOLITE USING CHIRAL SYNTHON
Details
A convenient and stereoselective synthetic method of vitamin D_3 metabolites having a chiral center on the side chain, has been deviced using chirality transfer method. In this method, the target molecule is constructed from two parts, namely, steroid skeleton and the side chain. The C-22 steroid alcohol(6a), which was conveniently obtained from ergosterol by Barton's method, was chosen as a common precursor of steroid skeleton and was used after being converted to the phenylsulfonyl derivative(6d). As a precursor of the side chain, the appropriate natural chiral molecule with desired stereochemistry was chosen. Applying this method, (24R)-24,25-dihydroxyvitamin D_3(1) was synthesized stereoselectively and efficiently (in 17% overall yield from 6d) using D-glyceric acid as a chiral synthon to construct the side chain. Synthesis of (25R)-25,26-dihydroxyvitamin D_3(2) was also examined and was partially achieved employing the same steroid precursor(6d) as used in the synthesis of 1 and citramalic acid as a precursor of the side chain.
