Ab initio multi-dimensional conformational analysis of R-(-)-desmethyldeprenyl: A potent neuroprotective metabolite of R-(-)-deprenyl

摘要

R-(-)-desmethyldeprenyl, a primary metabolite of R-(-)-deprenyl, has been shown to have more potency in neuroprotection then its parent compound. Since some of R-(-)-deprenyl's efficacy has been attributed to R-(-)-desmethyldeprenyl, the stereochemical surface of N-protonated R-(-)-desmethyldeprenyl was scanned via Multi Dimentional Conformational Analysis (MDCA) using gas phase molecular orbital (MO) calculations at Restricted Hartree Fock RHF/3-21G using Gaussian 98 to identify highly occupied conformations and to divulge its conformational characteristics. Results indicated a dominant gauche effect at chi(1), where the gauche orientation is always preferred over the syn/anti. Torsion chi(2) dictates the presence of proton benzene interactions; when chi(2) is equal to anti both amine protons of N-protonated R-(-)-desmethyldeprenyl are oriented such that they cannot form intramolecular attractive forces (IMAF) with the benzene ring. Furthermore, energetics indicates that H29-C6 IMAF is favoured over H29-C1, H26-C6 and H26-C1 IMAF's. Torsion chi(4) of N-protonated R(-)-desmethylselegiline predicts proton carbon-carbon triple bond interactions. (c) 2005 Elsevier B.V. All rights reserved.