Pyruvic Acid ketimine

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

Figure 19-10. The pyruvate formation with the N-terminal cysteine. The C-2 carbonyl in pyruvic acid initially forms a ketimine intermediate (A). The sulfhydryl (SH) group of Cys-1 generated from the reduced cysteine 1-98 disulfide bond in Iso tends to favor the formation of the more thermodynamically stable cyclic thiazoUdiae pyruvate intermediate (B).

Fig. 67. Equilibrium between pyruvic acid and glycine. Dependence of the wave-height of the more positive (ketimine) wave (t) expressed as the ratio ijid on the glycine concentration.

It has been known for a long time that nature has employed a reductive amination protocol in biological systems. Transferase enzymes use hydrogen bonding to activate pyruvate-derived ketimines selectively toward hydride delivery from NADH, thereby ensuring the enantiocontroUed formation of naturally occurring amino acids. 

Having successfully accelerated the reversible isomerization between the aldimine and ketimine Schiff bases, Murakami et al. then studied how to obtain turnovers in the full transamination reaction between one amino acid and one keto acid [25]. They found that the bilayer vesicle system constituted with 33, 36, and Cu(n) ions showed some turnovers for the transamination between L-phenylalanine and pyruvic add. However, such turnover behavior was not observed in a vesicular system composed of 32, 36, and Cu(n) ions, and an aqueous system involving N-methylpyridoxal and Cu(n) ions without amphiphiles. Therefore, both the hydrophobic effect and the imidazole catalysis effect were proposed as important for the turnover behavior. 

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