[摘要]：The Delta(16) structure as a vitamin D analog enhanced vitamin D receptor (VDR) binding affinity and induced significant cell differentiation, whereas its relative calcemic activity was reduced compared to 1 alpha,25-dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)). Methodologies available to introduce a double bond at C16-C17 of the D-ring on the seco-steroidal skeleton were limited; therefore, a new synthetic strategy was developed to obtain not only the Delta(16) structure, but also a new C15 functional group. Since C15-functionalization was unprecedented in vitamin D analog studies, the hybrid structure of Delta(16) and the C15-OH group at the D-ring may provide important information on the structure-activity relationship with vitamin D analogs. The synthesized 16-ene-2 alpha-methyl-1 alpha,15 alpha,25-trihydroxyvitamin D(3) showed almost 3-times higher VDR binding affinity and an equipotent level of osteocalcin promoter transactivation activity in human osteosarcoma cells as compared to 1 alpha,25(OH)(2)D(3).
