SOLVENT DEPENDENCE OF OPTICAL-ROTATION OF ][1,4]BENZODIAZEPINE-3-YL]-1H-INDOLE-2-CARBOXAMIDE

A new cholecystokinin-A antagonist, (S)-N-[l orophe-nyl)-3,4,6,7-tetra hydro-4-oxo-pyrrolo[3,2,1 ][1,4]benzodiazepine-3-yl]-1H-indole-2-carbo xamide (FR120480; 1), is a chiral compound that shows considerable sol vent dependence of its optical rotation. Not only the absolute values, but also the signs (+ or -) for this compound change in various solve nts. The optical rotation of 1 inherently correlated to the electron d onating property characterized by donor number of the solvent. The H-1 NMR study implied that hydrogen bonds were formed between electron do nor groups of the solvents and the NH groups of indole and amide of 1. In accordance with the NMR results, X-ray crystallography of the tetr ahydrofuran solvate of 1 showed that hydrogen bond formation occurred between the oxygen atom of tetrahydrofuran and the amide group of 1.