Novel Synthetic Approach to 1alfa,25-Dihydroxyvitamin D3 and Analogues

M. MAESTRO, C. GÓMEZ-REINO, D. NICOLETTI, R. SIGÜEIRO, R. FRAGA, A.A GHINI, M TORNEIRO AND A MOURIÑO

Victoria, British Columbia, Canada

Congreso; 13th Workshop on Vitamin D; 2006

The Vitamin D Workshop, Inc

A mild and stereoconvergent synthesis of 1alfa,25-dihydroxyvitamin D3 (calcitriol, 1a) is described. The key step is a cascade process consisting of two consecutive transformations: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflate 4 followed by a Negishi cross-coupling reaction with alkenyl zinc 3. This approach is of interest for the rapid synthesis of a variety of new vitamin D3 analogues of therapeutic potential, especially those modified at the triene and ring-A. The mildness of the method also allows the preparation of thermal sensitive vitamin D3 analogues.