Application of Threonine Aldolases for the Asymmetric Synthesis of α-Quaternary α-Amino Acids

Overview

Journal ChemCatChem

Date 2019 May 7

PMID 31057675

Citations 6

Authors

Julia Blesl

Melanie Trobe

Felix Anderl

Rolf Breinbauer

Gernot A Strohmeier

Kateryna Fesko

Affiliations

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Abstract

We report the synthesis of diverse β-hydroxy-α,α-dialkyl-α-amino acids with perfect stereoselectivity for the α-quaternary center through the action of l- and d-specific threonine aldolases. A wide variety of aliphatic and aromatic aldehydes were accepted by the enzymes and conversions up to >80 % were obtained. In the case of d-selective threonine aldolase from sp., generally higher diastereoselectivities were observed. The applicability of the protocol was demonstrated by performing enzymatic reactions on preparative scale. Using the d-threonine aldolase from sp., (2,3)-2-amino-3-(2-fluorophenyl)-3-hydroxy-2-methylpropanoic acid was generated in preparative amounts in one step with a diastereomeric ratio >100 favoring the -product. A Birch-type reduction enabled the reductive removal of the β-hydroxy group from (2)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-α-methyl-phenylalanine via a two-step chemo-enzymatic transformation.

Citing Articles

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