SYNTHESIS OF 1α,25-DIHYDROXY-2β-(3-HYDROXYPROPOXY)VITAMIN D3 (ELDECALCITOL) AND RELATED COMPOUNDS BY THE TROST CONVERGENT METHODOLOGY

Using Trost convergent methodology, the synthesis of 1 alpha,25-dihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (eldecalcitol) for the improved and industrial scale production and related putative metabolites of eldecalcitol is summarized. In addition, A-ring diastereomers at the 1- and 3-positions of eldecalcitol are described. The synthesis centers on a key palladium-catalyzed alkylative cyclization and coupling of ene-ynes that constitute the A-ring fragment to bromomethylenes comprising the C/D-ring fragment which affords the requisite triene framework of vitamin D-3 analogs.