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

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 C==N bond. Due to the structural difference and the increase in acidity of the alpha 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 alpha 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.

Deracemization of Racemic Amino Acids Using (R)- and (S)-Alanine Racemase Chiral Analogues as Chiral Converters

“…Table 2 shows some comparative stereoselective results determined by both the achiral HPLC and NMR methods (entry 7, 9, 10, and 14). 2,5 Comparison of the achiral HPLC and NMR analysis shows somewhat different stereoselectivities, which might be due to the intrinsic features of the relatively less accurate NMR analytical method. Since only deuterated NMR solvents should be used in this technique for the reaction and no overlapped NMR peaks for the diastereomer ratio should exist in resulting NMR spectra, we find that the HPLC method is much more accurate and convenient than NMR for this analysis.…”

“…[2][3][4][5] Since (S)-ARCA showed a higher stability with D-amino acids than with L-amino acids, several L-amino acids were preferentially converted to D-amino acids via (S)-ARCA/D-amino acid imine diastereomer formation. For the deracemization process undertaken in this study, we utilized both (R)-ARCA and (S)-ARCA as chiral converters, which were expected to generate L-and D-amino acids, respectively, from the starting racemic mixtures.…”

Binol Based Chirality Conversion Reagents for Underivatized Amino Acids

“…Earlier, we showed several binol based receptors as able CCR's which convert amino acids [17]- [19] and peptides [20] [21] from L-form to D-form by the reversible imine formation [22] [23]. Multiple hydrogen bonding dur-ing the imine formation along with internal Resonance-Assisted H-bonds (RAHBs) play important roles in de-termining the stereoselective ratio (D/L) during the Chirality Conversion (CC).…”

Enantioselective Recognition of Amino Alcohols and Amino Acids by Chiral Binol-Based Aldehydes with Conjugated Rings at the Hydrogen Bonding Donor Sites

“…In efforts to acquire more effective enantiomeric selectivities, we modified the receptor's HBD to pyrroles, diuryls etc., which brought about versatile enantioselectivities for aminoalcohols and peptides besides amino acids. [6][7][8][9][10] In this context, we tried to introduce conjugated ring systems at the periphery of the uryl and guanidium groups as shown in Figure 1 to alter the strength of the hydrogen bonding and to study its effect on the stereoselectivities of amine substrates. Here we report the detailed syntheses of new binol-based aldehydes with ring conjugated systems along with comparison of receptors 1-6 for their stereoselectivities to amino alcohols and amino acids as CCRs.…”