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

作者：Blesl Julia; Trobe Melanie; Anderl Felix; Breinbauer Rolf; Strohmeier Gernot A; Fesko Kateryna^*

来源：ChemCatChem, 2018, 10(16): 3453-3458.

DOI：10.1002/cctc.201800611

• Amino acids
• Asymmetric catalysis
• Enzyme catalysis
• Quaternary stereogenic centers
• Threonine aldolases

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.

• 出版日期2018-8-21