Development of a Donor−Acceptor Concept for Enzymatic Cross-Coupling Reactions of Aldehydes:  The First Asymmetric Cross-Benzoin Condensation

“…However, little use of BAL to couple dissimilar aromatic aldehydes has been reported. [12] While 2-hydroxybenzaldehyde is a poor substrate with BAL, [13] the corresponding 2-methoxybenzaldehydes do condense to form acyloins. [7] Thus, we examined BALcatalyzed, mixed acyloin reactions with phenylacetaldehyde and variously substituted methoxybenzaldehydes (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Mixed Aromatic Acyloin Condensations with Recombinant Benzaldehyde Lyase: Synthesis of α‐Hydroxydihydrochalcones and Related α‐Hydroxy Ketones

Sanchez‐Gonzalez¹,

Rosazza²

2003

Adv Synth Catal

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Recombinant benzaldehyde lyase (BAL), expressed and purified from E. coli strain JM-109, was used to catalyze the condensation of a series of methoxybenzaldehydes and phenylacetaldehyde in the synthesis of a-(R)-hydroxydihydrochalcones. Enantiomerically pure 1-hydroxy-1,3-diphenylpropan-2-ones and o-anisoin were also obtained as products of the BAL reaction. The R absolute configurations of chiral centers were determined by CD spectroscopy. a-(R)-Hydroxydihydrochalcones and 1-hydroxy-1,3-diphenylpropan-2-ones are valuable synthons for chemoenzymatic syntheses of flavonoids. This is the first synthesis of a-(R)-hydroxydihydrochalcones by a microbial enzyme.

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“…It is conceivable that this change could reduce proton transfer efficiency, resulting in an increase in the lifetime of the carbanion/enamine. It is well known that the BFDC H281A variant has been associated with an improvement in carboligation efficiency [49][50][51], which was attributed to the longer lifetime of the enamine. It is also notable that an increase in the lifetime of the carbanion/enamine in ZmPDC gave rise to formation of acetoin/acetolactate [52].…”

Section: X-ray Structure Of Bfdc T377l/a460ymentioning

confidence: 99%

Mechanistic and Structural Insight to an Evolved Benzoylformate Decarboxylase with Enhanced Pyruvate Decarboxylase Activity

et al. 2016

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Benzoylformate decarboxylase (BFDC) and pyruvate decarboxylase (PDC) are thiamin diphosphate-dependent enzymes that share some structural and mechanistic similarities. Both enzymes catalyze the nonoxidative decarboxylation of 2-keto acids, yet differ considerably in their substrate specificity. In particular, the BFDC from P. putida exhibits very limited activity with pyruvate, whereas the PDCs from S. cerevisiae or from Z. mobilis show virtually no activity with benzoylformate (phenylglyoxylate). Previously, saturation mutagenesis was used to generate the BFDC T377L/A460Y variant, which exhibited a greater than 10,000-fold increase in pyruvate/benzoylformate substrate utilization ratio compared to that of wtBFDC. Much of this change could be attributed to an improvement in the K m value for pyruvate and, concomitantly, a decrease in the k cat value for benzoylformate. However, the steady-state data did not provide any details about changes in individual catalytic steps. To gain insight into the changes in conversion rates of pyruvate and benzoylformate to acetaldehyde and benzaldehyde, respectively, by the BFDC T377L/A460Y variant, reaction intermediates of both substrates were analyzed by NMR and microscopic rate constants for the elementary catalytic steps were calculated. Herein we also report the high resolution X-ray structure of the BFDC T377L/A460Y variant, which provides context for the observed changes in substrate specificity.

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Development of a Donor−Acceptor Concept for Enzymatic Cross-Coupling Reactions of Aldehydes: The First Asymmetric Cross-Benzoin Condensation

Abstract: Highly enantioenriched mixed benzoins are obtained selectively through a biocatalytical cross-coupling reaction of aromatic aldehydes using ThDP-dependent enzymes.

Cited by 228 publications

References 14 publications

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Mixed Aromatic Acyloin Condensations with Recombinant Benzaldehyde Lyase: Synthesis of α‐Hydroxydihydrochalcones and Related α‐Hydroxy Ketones

Mechanistic and Structural Insight to an Evolved Benzoylformate Decarboxylase with Enhanced Pyruvate Decarboxylase Activity

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