N-primary-amine-terminal beta-turn tetrapeptides as organocatalysts for highly enantioselective aldol reaction.
Tetrapeptides, containing a terminated primary amine and conformationally restricted D-Pro-Gly or D-Pro-Aib (2-aminoisobutanoic acid) segment as a strongly beta-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 intensive beta-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). The asymmetric induction in the reaction of hydroxyacetone was not affected by solvents, and predominant anti products were achieved by 1g in MeCN with the additive (S)-BINOL.
Wu
Feng-Chun
FC
Institute of Biochemistry & Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
Da
Chao-Shan
CS
Du
Zhi-Xue
ZX
Guo
Qi-Peng
QP
Li
Wei-Ping
WP
Yi
Lei
L
Jia
Ya-Ning
YN
Ma
Xiao
X
D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D004151:Dipeptides / Q000737:chemistry*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D013237:Stereoisomerism
D000447:Aldehydes; D000588:Amines; D004151:Dipeptides; D009842:Oligopeptides; C057749:prolylglycine