EXPLORING POTENTIAL-ENERGY HYPERSURFACES FOR TRIPLE SYMMETRICAL INVERSION IN 3-AZABICYCLO[3.3.1]NONAN-9-ONE AND ITS N-METHYL DERIVATIVE

The potential energy hypersurfaces for the triple inversion, from chai r to boat and alpha to beta conformations, are explored theoretically in 3-azabicyclo[3.3.1]nonan-9-one and its N-methyl derivative, by usin g ab initio quantum-mechanical calculations. Both compounds are precur sors of rigid analogs of the potential GABA(A) and GABA(B) receptor an tagonists. In contrast to results from semiempirical calculations, the chair-chair beta conformers are found to be, by far, the most stable structures for both the nonmethylated and N-methylated compounds. The inversion barriers are found to be relatively low, so that the conform ers could be expected to exist in thermodynamic equilibrium at room te mperature. A population analysis reveals, however, that, in the ab ini tio approach, the molecules seem to exist practically only in the chai r-chair-beta conformation. The theoretical results compare well with t he available experimental data. (C) 1998 John Wiley & Sons, Inc.