Conformational behavior on 2,2,3-trisubstituted 1,2,3,4-tetrahydroquinoline alkaloids, virantmycin, benzastatins, and their congeners, evaluated by semi-empirical molecular orbital calculations

The conformational behaviors on ring inversion between two half-chair conformers ii and b in physiologically active 2,2,3-trisubstituted 1,2,3,4-tetrahydroquinoline alkaloids, virantmycin (1), benzastatin C (6), benzastatin D (7), and their congeners 2-5, which were revealed by their nmr studies have been quantitatively evaluated by semiempirical molecular orbital calculations (PM3). The geometries of respective half-chair conformers a and b in compounds 1-7 were optimized and it was found that their thermodynamic distributions are approximately valid in comparison with the coupling constants observed in their nmr experiments. Furthermore, these calculations estimated the energy barriers for ring inversion in compounds 1-7 in the range of ca. 4.86-11.13 kcal/mol, which were compatible with rapid interconversions between a and b at room temperature.