Stereoselective synthesis of 1β,25-Dihydroxyvitamin D3 and its 26,27-hexadeuterated derivative

A mild convergent synthesis of 1 beta,25-dihydroxyvitamin D-3 (3a), a metabolite of vitamin D-3, and its C26,27-hexadeuterated derivative (3b) are described. The A-ring and the CD-fragments are constructed from (R)-carvone and Inhoffen-Lythgoe diol, respectively. The triene system is assembled by a Pd(0)-catalyzed process, which involves an enol-triflate (A-ring fragment) and an alkenyl boronate (CD-side chain fragment). Deuterium labeling is introduced at the last step of the synthesis. (C) 2015 Elsevier Ltd. All rights reserved.