ABSTRACT
Theoretical investigations of the transition structures of additions and cycloadditions reveal details about the geometries of bond-forming processes that are not directly accessible by experiment. The conformational analysis of transition states has been developed from theoretical generalizations about the preferred angle of attack by reagents on multiple bonds and predictions of conformations with respect to partially formed bonds. Qualitative rules for the prediction of the stereochemistries of organic reactions have been devised, and semi-empirical computational models have also been developed to predict the stereoselectivities of reactions of large organic molecules, such as nucleophilic additions to carbonyls, electrophilic hydroborations and cycloadditions, and intramolecular radical additions and cycloadditions.
Subject(s)
Chemistry, Organic , Models, Chemical , Molecular Conformation , Organic Chemistry PhenomenaABSTRACT
This paper correlates the X-ray structures of two 4-(beta-1-naphthylvinyl)pyridine analogues (one cis and one trans) with chemical and biological activity data for this class of cholineacetylase inhibitors. Our results suggest that one of the two proposed mechanisms for inhibition by this class of compounds better describes their efficacy. Previous arguments about coplanarity of the aromatic rings and nucleophilicty across the vinyl linkage need to be modified. Quantum calculations are also included and substantiate previous suggestions about the charge distribution across the vinyl linkages. An alternate new mechanism of inhibition is proposed to encompass the published data and more recent results discussed in this paper.
