Peptides With β-Turn Secondary Structure As Enzyme Mimics For Asymmetric Aldol Reactions

Synthetic peptides with higher conformation structures,which were usually used as enzyme mimics in many organic reactions,have great theoretic and application values in explaining the mechansim and expanding the scope of enzyme catalysis. Tetrapeptides,containing a terminated primary amine and conformationally restricted D-Pro-Gly or D-Pro-Aib(2-aminoisobutanoic acid) segment as a stronglyβ-turn-nucleating element,were designed and synthesized with condensation of N-module dipeptides with C-module dipeptides in solution.They were first applied to catalyze aldol reactions,and were found to be effective catalysts for the transformations.The tetrapeptide Val-D-Pro-Gly-Leu-OH(1g) was the optimal organocatalyst.It was shown that the intensiveβ-turn conformation,indicated by CD and NOESY spectra,contributed to the(R)-aldol and high enantioselectivity of the reaction of acetone in MeOH whereas the sharply varied conformation should contribute to the low enantioselectivity and(S)-product of the reaction in 1,2-dichloroethane(DCE).It is interesting that the asymmetric induction in the reaction of hydroxyacetone was not affected by solvents.Secondary structures of the tetrapeptide which are greatly depended upon the varied solvents could not surprisingly have effects on the asymmetric induction on account of the strong behavior of hydroxyacetone in the reaction.And predominant anti products were achieved by Val-D-Pro-Gly-Leu-OH(1g) in MeCN with the additive BINOL.