Synthetic studies of (23S,25R)-1α,25-dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) and its derivatives

(23S,25R)-1α,25-Dihydroxyvitamin D3 26,23-lactone (calcitriol lactone) is a major metabolite of 1α,25-dihydroxyvitamin D3 that binds to vitamin D receptor (VDR) and exhibits various biological activities. This lactone and its derivatives are considered to have potential as drug candidates to treat VDR-related diseases, but their biological activities have not yet been fully characterized, mainly because of their limited availability by chemical synthesis. This review deals with synthetic studies of calcitriol lactone, and its derivatives, i.e., methylene lactones (TEI-9647 and its derivatives) and calcitriol lactams (DLAMs). We also discuss their biological activities, VDR-binding affinity and structure-activity relationships.