Studies on asymmetric induction associated with the coupling of N-acylamino acids and N-benzyloxycarbonyldipeptides.
The asymmetric induction occurring during aminolysis by an amino acid benzyl ester of the 5(4H)-oxazolones obtained from N-acyl-DL-valine for acyl = formyl, acetyl, benzoyl, trifluoroacetyl and N-benzyloxycarbonyl-Xaa where Xaa = Gly, Ala and Leu in dichloromethane and dimethylformamide at +5 degrees and -5 degrees was determined by analysis of the epimeric products by high-performance liquid chromatography after removal of protecting groups by hydrogenolysis. The influence of the side-chain of the activated residue on induction was assessed by examining aminolysis of the 5(4H)-oxazolones from N-benzyloxycarbonyl glycyl-Xaa-OH for Xaa = Ala, Leu, Val, and Phe. The contribution of induction to the epimeric content of products obtained from couplings mediated by N,N'-dicyclohexylcarbodiimide in the presence and absence of l-hydroxybenzotriazole, and by the mixed-anhydride method, were calculated. The induction was affected at varying levels by the nature of the N-acyl group, the side-chain of Xaa, the nature of the aminolyzing nucleophile, the nature of the solvent, and the temperature, with diastereomeric excesses reaching -32 and +53. The influence of the side-chain of Xaa on the induction was different in the two solvents. For the N-acyl series, the epimeric content of products did not always correctly reflect the relative tendencies of the derivatives to racemize. The order for epimeric content of the products also depended on the method of coupling.
Benoiton
N L
NL
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Lee
Y C
YC
Chen
F M
FM
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D004151:Dipeptides; D010455:Peptides