A semiempirical study of the conformational behavior of cinchonidine and its interaction with methyl pyruvate

Hydrogenation of methyl pyruvate on a palladium or platinum surface in the presence of cinchona alkaloids leads to a high degree of enantiodifferentia tion. In the present study, the semiempirical AMI and PM3 methods are emplo yed to perform a detailed analysis of the conformational behavior of cincho nidine and to study its interaction with methyl pyruvate. Nine different mi nima were located on the potential energy surface for cinchonidine by both the AM I and the PM3 methods. Some barriers to interconversion between them are relatively hi gh; however, it is always possible to connect two minima through barriers lower than 3.0 kcal/mol so most of the minima can interac t with the substrate. The interaction between cinchonidine and methyl pyruv ate was calculated by placing methyl pyruvate near the cinchonidine molecul e in different orientations and optimizing the final complex. The calculate d interaction energy is lower than 3.5 kcal/mol and is predominantly due to van der Waals noncovalent interactions. An analysis of the structure of po ssible pro-R and pro-S complexes indicates that interaction between cinchon idine and methyl pyruvate alone is not enough to induce enantiodifferentiat ion.