Computational support for the 'double activation' mechanism of macrolide ring closure

摘要

The ring closure reaction, used to generate the macrocyclic lactones by the 'double activation' mechanism, was studied by ab initio method (RHF/6-31G~* and RHF/6-31 + G~(**)). Two possible transition states (anti and syn) of a simplified model system were determined by the ab initio calculations. The activation energy of the reaction was estimated to be in the range of 30-37 kcal mol~(-1), depending on the syn and anti orientation of the reactive groups as well as on the inclusion or omission of ZPV energy. Single point MP2 computations lowered the barrier heights substantially. The implications of these results are discussed.