Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D Analogues and Their Stability to hCYP24A1-Dependent Catabolism.

Two 24-fluoro-25-hydroxyvitamin D analogues (,) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24)- and (24)-24-fluoro-25-hydroxyvitamin D revealed that the C24--configuration isomer was more resistant to CYP24A1-dependent metabolism than its 24-isomer . The new synthetic route of the CYP24A1 main metabolite (24)-24,25-dihydroxyvitamin D () and its 24-isomer () was also studied using synthetic intermediates (,) in parallel.