ISSN:
0192-8651
Keywords:
polycyclic conformers
;
GABA rigid precursor analogs
;
conformer population analysis
;
comparison between ab initio, AM1, and MM2 calculations
;
Chemistry
;
Theoretical, Physical and Computational Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Computer Science
Notes:
The potential energy hypersurfaces for the triple inversion, from chair to boat and α to β conformations, are explored theoretically in 3-azabicyclo[3.3.1]nonan-9-one and its N-methyl derivative, by using ab initio quantum-mechanical calculations. Both compounds are precursors of rigid analogs of the potential GABAA and GABAB receptor antagonists. In contrast to results from semiempirical calculations, the chair-chair β 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 conformers could be expected to exist in thermodynamic equilibrium at room temperature. A population analysis reveals, however, that, in the ab initio approach, the molecules seem to exist practically only in the chair-chair-β conformation. The theoretical results compare well with the available experimental data. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1567-1574, 1998
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
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