Abstract
On the basis of conformational analysis of the side chain of 1, 25-(OH)_2D_3 (1) and its 20-epimer (2), we grouped region in space, where the side chain of these vitamin D can move about, into four, A, G, EA and EG. We then designed and synthesized analogs whose side chain mobility is restricted in one of these four regions: four diastereomers at C-20 and -22 of 22-methyl-1, 25-(OH)_2D_3 (3〜6). We evaluated various activities of these analogs (3〜6). The results lead us to delineate space group-activity relationship. We similarly analyzed the conformation of nearly fifty highly active known vitamin D analogs and defined another space region F. The results show that our active space group concept can be applicable to almost all these side chain analogs. Altogether, the following space group-activity relationship was found: VDR affinity, EA>A>F>G>EG; DBP affinity, A only; Cell differentiation, EA>F>A>EG and G; Calcemic, EA>A and G>F>EG.
