Amino acids and peptides—IV: Novel peptide bond formation catalysed by metal ions—II Formation of optically active peptide esters

The novel peptide bond formation previously reported in the reaction of glycine ester with Cu(II) ion in an anhydrous solvent, was examined using several kinds of optically active amino acid esters. Various reaction conditions were studied in detail for Phe-OEt. From Phe-OEt, Ala-OMe, Leu-OMe, Trp-OMe, Ser-OMe, and Met-OMe, the expected dipeptide esters with the same amino acid components were obtained without racemization. Asp(OEt)-OEt, and Glu(OMe)-OMe gave only optically active α-dipeptide esters. No formation of dipeptide esters was observed with Ile-OMe, Cys-OMe, His-OMe, and Pro-OEt. However, Lys-OMe, and Orn-OMe afforded optically active lactam derivatives. Some explanations of these abnormal observations have been given.Attempts to prepare di- and tri-peptide esters carrying different kinds of amino acid units were also studied.     

Amino acids and peptides—V: Novel peptide bond formation catalyzed by metal ions—III Elucidation of the formation mechanism

Elucidation of the mechanism for peptide bond formation observed when an amino acid ester is treated with anhyd CuCl₂ in an anhyd alcoholic solvent, was attempted using results of IR and visible spectra measurements of the amino acid ester-CuCl₂ complex and accumulated experimental data.This novel reaction proceeds through a mechanism in which the amino anion produced by elimination of the proton from the Cu(II)-coordinating amino group, attacks the non-activated ester CO group of the amino acid ester which shares a common Cu(II) ion. It differs completely from the peptide formation reaction featuring a Co(III)-amino acid ester complex.     

Resolution of amino acids on optically active stationary phase by gasChromatography

Summary The various enantiomeric esters of TFA--amino acid may be separated directly by gas chromatography on optically active stationary phase. In this work we investigated the resolution of relatively volatile amino acids (alanine, -amino-n-butyric acid, valine, threonine, allo-isoleucine, isoleucine, norvaline, leucine, proline, norleucine, serine) and less volatile amino acids (cysteine, aspartic acid, methionine, phenylalanine, glutamic acid) on a glass capillary column coated with N-caproyl-L-valyl-L-valine cyclohexyl ester.     

Amino acids and peptides. XXIII. Synthesis of N alpha-protected amino acid 6-chloro-2-pyridyl esters and their evaluation for peptide synthesis

6-Chloro-2-pyridyl esters (OPyCl) of N alpha-benzyloxycarbonyl and tert-butyloxycarbonylamino acids were synthesized by the N,N'-dicyclohexylcarbodiimide (DCC) method from the acids and 6-chloro-2-hydroxypyridine in dimethylformamide (DMF). The reactivity of the 6-chloro-2-pyridylester with amino group is much higher than that of the corresponding 2-pyridyl ester (OPy) and p-nitrophenyl esters (ONp) in dioxane and DMF, and a peptide bond is formed without acylation at the side chain hydroxyl group of amino acids. Z-Asp(OBzl)-OPyCl reacted with amino acid methyl esters in dioxane to give the corresponding dipeptide without any detectable aspartimide formation.     

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.     

Enantioselectively catalyzed hydrolysis of p-nitrophenyl esters of N-protected L or D-amino acids by optically active hydroxamic acid and dipeptides

Catalyzed hydrolysis of p-nitrophenyl esters of N-protected L or D-phenylalanine by optically active hydroxamic acid or dipeptides in the presence of CTABr micelles showed high enantioselectivity (D/L=5.68 for L-ZLysZ(MHX)), demonstrating control of the direction of the enantioselectivity based on the balance of the structures of the nucleophile and substituent.