Functional group requirements within the peptide H-Pro-Pro-Asp-NH2 as a catalyst for aldol reactions

H-Pro-Pro-Asp-NH2 1 is a versatile catalyst for asymmetric aldol reactions. In this work, the functional group tolerance within the catalyst structure has been examined. Several analogs of H-Pro-Pro-Asp-NH2 in which the N-terminal secondary amine or the carboxylic acid in the side chain of the aspartic acid residue is replaced by different functional groups were prepared. Evaluation of their catalytic properties revealed that both the N-terminal secondary amine and the carboxylic acid are important for catalysis. The implications for the reaction mechanism are discussed.