Structure and Conformations of Gaba-Transaminase Inhibitors. II. Transition-State Analogs

Abstract

Crystal structures of two benzoxazine derivatives designed as transition state analogue inhibitors of GABA-T were determined. These cyclic oxazine structures are shown to be more similar to the proposed transition state than the pyridoxal derivatives reported in the preceding article.1 Conformational analyses (non-bonded energy, MINDO/3, MNDO) show that the crystal structures are close to the calculated energy minima. The MNDO parameterization gives geometries close to the crystal structure, with the configuration at the nitrogen of the oxazine ring in particular being better reproduced than by the MINDO/3 method, which tends to prefer planar (sp2) nitrogen.