Remarkable effect of 2[small alpha]-modification on the VDR antagonistic activity of 1small alpha-hydroxyvitamin D3-26,23-lactones

Novel 2small alpha]-methyl-, 2small alpha]-(3-hydroxypropyl)- and 2small alpha]-(3-hydroxypropoxy)-substituted 25-dehydro-1small alpha]-hydroxyvitamin D-26,23-lactone derivatives were efficiently synthesized Reformatsky type allylation and palladium-catalyzed alkenylative cyclization processes, and their biological activities were evaluated. Introducing functional groups into the 2small alpha]-position of the vitamin D-26,23-lactones resulted in remarkable enhancement of their antagonistic activity on vitamin D receptor (VDR).