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Stereoconversion of Amino Acids and Peptides in Uryl‐Pendant Binol Schiff Bases
Author(s) -
Park Hyunjung,
Nandhakumar Raju,
Hong Jooyeon,
Ham Sihyun,
Chin Jik,
Kim Kwan Mook
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801036
Subject(s) - imine , deprotonation , protonation , chemistry , amino acid , stereochemistry , hydrogen bond , alanine , intramolecular force , medicinal chemistry , schiff base , molecule , organic chemistry , catalysis , ion , biochemistry
Abstract ( S )‐2‐Hydroxy‐2′‐(3‐phenyluryl‐benzyl)‐1,1′‐binaphthyl‐3‐carboxaldehyde ( 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 CN bond. Due to the structural difference and the increase in acidity of the α proton of the amino acid, the imine formed with an L ‐amino acid ( 1 –l ‐aa) is converted into the imine of the D ‐amino 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 α proton of alanine in the imine form was studied by 1 H NMR spectroscopy and the results support a stepwise mechanism in the L ‐into‐ D conversion rather than a concerted one; that is, deprotonation 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 1 and the predominantly D ‐form amino acid can be recovered from the imine by simple extraction under acidic conditions. Hence, 1 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.