1α,25-Dihydroxyvitamin D3(1) has a wide range of biological activities, for example, calcium and phosphorus homeostasis, cell growth and differentiation. The actions of 1 are mediated by a specific nuclear receptor, vitamin D receptor (VDR). Hydrogen bonds between three hydroxyl groups of 1 and hydrophilic amino acids in the ligand-binding domain (LBD) of VDR are essential for its actions. Arginine 274 is known to form hydrogen bond with 1α-OH of 1, and its mutation lead to loss of the affinity and its actions. For the mutant VDR we designed the analogs having a CH3 or HOCH2 group on its 1α-position to effect hydrophobic interaction. A coupling reaction of CD ring bromoolefin and A ring enyne was carried out by the method developed by Trost. A ring enynes for 1α-CH3 and 1α-HOCH2 analogs were prepared from D-galactose and D-glucose, respectively.
