Stereoconversion of Amino Acids and Peptides in Uryl-Pendant Binol Schiff Bases

Abstract

(S)-2-Hydroxy-2'-(3-phenyl-uryl-benzyl)-1,1'-binaphthyl-3-carboxal- dehyde (1) forms Schiff bases with a wide range of nonderivatized amino acids, including unnatural ones. Multiple hydrogen bonds, including resonance-assisted ones, fix the whole orientation of the imine and provoke structural rigidity around the imine C=N bond. Due to the structural difference and the increase in acidity of the cc proton of the amino acid, the imine formed with an L-amino acid (1-L-aa) is converted into the imine of the Damino acid (1-D-aa), with a D/L ratio of more than 10 for most amino acids at equilibrium. N-terminal amino acids in dipeptides are also predominantly epimerized to the D form upon imine formation with 1. Density functional theory calculations show that 1-D-Ala is more stable than 1-L-Ala by 1.64 kcal mol(-1), a value that is in qualitative agreement with the experimental result. Deuterium exchange of the alpha proton of alanine in the imine form was studied by H-1 NMR spectroscopy and the results support a stepwise mechanism in the L-into-D conversion rather than a concerted one; that is, de-protonation and protonation take place in a sequential manner. The deprotonation rate of L-Ala is approximately 16 times faster than that Of D-Ala. The protonation step, however, appears to favor L-amino acid production, which prevents a much higher predominance of the D form in the imine. Receptor I and the predominantly D-form amino acid can be recovered from the imine by simple extraction under acidic conditions. Hence, I is a useful auxiliary to produce D-amino acids of industrial interest by the conversion of naturally occurring L-amino acids or relatively easily obtainable racemic amino acids.