Synthesis, Configuration, and Calcium Modulatory Properties of Enantiomerically Pure 5-Oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates

Article abstract of DOI:10.1021/jm00090a014

Enantiomerically pure hexahydroquinolinones of the structural type 9 were prepared by a variation of the Hantzsch synthesis in which an optically active acetoacetate served as a chiral auxiliary reagent.Determination of the de and ee values are described.The absolute configurations of the optically pure products were characterized by single-crystal X-ray analysis.The antipodes 9a and 9b exhibited calcium antagonistic activities on smooth musculature; the (S)-(-)-enantiomer 9b was the more potent compound with regard to the EC50 values which differed by a factor of 100; the intrinsic axctivity of 9b was 1.2, compared with a value of 0.54 for 9a.On the other hand, R-(+)-9a exerted positive inotropic effects on electrically stimulated atria.The cause of these effects is discussed.