Direct asymmetric intermolecular aldol reactions catalyzed by amino acids and small peptides.
In nature there are at least nineteen different acyclic amino acids that act as the building blocks of polypeptides and proteins with different functions. Here we report that alpha-amino acids, beta-amino acids, and chiral amines containing primary amine functions catalyze direct asymmetric intermolecular aldol reactions with high enantioselectivities. Moreover, the amino acids can be combined into highly modular natural and unusual small peptides that also catalyze direct asymmetric intermolecular aldol reactions with high stereoselectivities, to furnish the corresponding aldol products with up to >99 % ee. Simple amino acids and small peptides can thus catalyze asymmetric aldol reactions with stereoselectivities matching those of natural enzymes that have evolved over billions of years. A small amount of water accelerates the asymmetric aldol reactions catalyzed by amino acids and small peptides, and also increases their stereoselectivities. Notably, small peptides and amino acid tetrazoles were able to catalyze direct asymmetric aldol reactions with high enantioselectivities in water, while the parent amino acids, in stark contrast, furnished nearly racemic products. These results suggest that the prebiotic oligomerization of amino acids to peptides may plausibly have been a link in the evolution of the homochirality of sugars. The mechanism and stereochemistry of the reactions are also discussed.
Córdova
Armando
A
Department of Organic Chemistry, The Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden. acordova@organ.su.se
Zou
Weibiao
W
Dziedzic
Pawel
P
Ibrahem
Ismail
I
Reyes
Efraim
E
Xu
Yongmei
Y
D000447:Aldehydes / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D002021:Buffers; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004121:Dimethyl Sulfoxide; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry*; D012996:Solutions; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis
D000447:Aldehydes; D000596:Amino Acids; D002021:Buffers; D007202:Indicators and Reagents; D010455:Peptides; D012996:Solutions; D012997:Solvents; D014297:Trimethylsilyl Compounds; C116609:3-hydroxybutanal; D004121:Dimethyl Sulfoxide