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Application of Threonine Aldolases for the Asymmetric Synthesis of α‐Quaternary α‐Amino Acids
Author(s) -
Blesl Julia,
Trobe Melanie,
Anderl Felix,
Breinbauer Rolf,
Strohmeier Gernot A.,
Fesko Kateryna
Publication year - 2018
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201800611
Subject(s) - enantiopure drug , aldolase a , chemistry , threonine , diastereomer , amino acid , stereochemistry , enantioselective synthesis , enzyme , stereoselectivity , phenylalanine , organic chemistry , catalysis , biochemistry , serine
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 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., (2 R ,3 S )‐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 β‐hydroxy group from (2 S )‐2‐amino‐3‐hydroxy‐2‐methyl‐3‐phenylpropanoic acid to generate enantiopure l ‐α‐methyl‐phenylalanine via a two‐step chemo‐enzymatic transformation.