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Application of Threonine Aldolases for the Asymmetric Synthesis of alpha-Quaternary alpha-Amino Acids
We report the synthesis of diverse beta-hydroxy-alpha,alpha-dialkyl-alpha-amino acids with perfect stereoselectivity for the alpha-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 Pseudomonas 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 Pseudomonas sp., (2R,3S)-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 syn-product. A Birch-type reduction enabled the reductive removal of the beta-hydroxy group from (2S)-2-amino-3-hydroxy-2-methyl-3-phenylpropanoic acid to generate enantiopure l-alpha-methyl-phenylalanine via a two-step chemo-enzymatic transformation.
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Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics