Synthesis and Biological Activities of Optical Isomers of 2-(4-Diphenylmethyl-1-piperazinyl)ethyl 5-(4, 6-Dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate Dihydrochloride (NIP-101)

Six optical isomers of 2-(4-diphenylmethyl-1-piperaziyl)ethyl 5-(4, 6-dimethyl-2-oxo-1, 3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydro-2, 6-dimethyl-4-(3-mitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101, 1·2HCl·2H2O), a potent calcium antagonist, were successfully prepared by using optically active (2R, 4R)-(-)- and (2S, 4S)-(+)-2, 4-pentanediols, and cis-2, 4-pentanediol and optically active (S)-(+)-2-methoxy-2-pheylethanol. Their proton nuclear magnetic resonance investigations demonstrate that the 1, 3, 2-dioxaphosphorinane group in conformationally constrained around the C-P bond. Calcium-antagonistic and hypotensive activities of the optical isomers were examined and found to depend mainly on the absoeute configuration at a stereogenic center in the 1, 4-dihydrophridine ring rather than the configuration of the 1, 3, 2-dioxaphospyorinane moiety.