- Kynureninase in organic synthesis : Preparation of γ-hydroxy-α-L-amino acids
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Kynureninase, which is known to catalyze the transaldol reaction between benzaldehyde and kynurenine, accepted many kinds of other aromatic aldehydes and propargyl aldehydes as the substrates to afford novel γ-hydroxy-α-L-amino acids. The L-configuration of the α-carbons was confirmed by an enzymatic method using both D- and L-amino acid oxidases. The stereochemistry of the newly formed chiral center (γ-position) in major isomers was determined to be R-configuration by the observed NOEs in the NMR spectroscopy of lactones derived from the γ-hydroxy-α-L-amino acids.
- Miura, Tsuyoshi,Masuo, Noriko,Fusamae, Yuki,Kajimoto, Tetsuya,Ida, Yoshiteru
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- Stereochemistry and mechanism of aldol reactions catalyzed by Kynureninase
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Kynureninase from Pseudomonas has been reported to catalyze aldol and retro-aldol reactions, in addition to the physiological hydrolytic cleavage of L-kynurenine to anthranilic acid and L-alanine. However, the stereochemistry of these novel aldol reactions has not been previously determined. We have determined that the reaction of L-kynurenine and benzaldehyde catalyzed by kynureninase results in (2S,4A)-2-amino-4-hydroxy-4-phenylbutanoic acid. Similarly, the 4R isomer of dihydro-L-kynurenine readily undergoes retro-aldol cleavage, while the 4S isomer is unreactive as a substrate. Both isomers of dihydro-L-kynurenine are competitive inhibitors of kynureninase from Pseudomonas. However, the 4S isomer of dihydro-L-kynurenine is the most potent inhibitor, with a Ki of 0.3 μM. These results provide additional support for a general base mechanism for kynureninase, and suggest that the hydration occurs on the re face of the carbonyl group of kynurenine to give an (S)-gem-diolate intermediate.
- Phillips, Robert S.,Dua, Rajesh K.
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p. 7385 - 7388
(2007/10/02)
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