Density functional theory study of the stereoselectivity in small peptide-catalyzed intermolecular aldol reactions

The origins of the stereoselection of the dipeptide-catalyzed intermolecular aldol reaction are explored by means of hybrid density functional theory. Transition states were located for the (S)-ala-(S)-ala-catalyzed aldol reaction with cyclohexanone as the donor and benzaldehyde as the acceptor. The calculations reproduce the experimental trends very satisfactorily. It is demonstrated that the main source of stereoselectivity is the interaction of the N-terminal amino acid side chain of the dipeptide with the cyclohexene ring.

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