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Chemoenzymatic Production of Enantiocomplementary 2‐Substituted 3‐Hydroxycarboxylic Acids from l ‐α‐Amino Acids
Author(s) -
Pickl Mathias,
MarínValls Roser,
Joglar Jesús,
Bujons Jordi,
Clapés Pere
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202100145
Subject(s) - chemistry , oxidative decarboxylation , aldol reaction , decarboxylation , oxidative deamination , amino acid , enantiomer , adduct , biocatalysis , deamination , hydrogen peroxide , organic chemistry , stereochemistry , catalysis , enzyme , biochemistry , reaction mechanism
A two‐enzyme cascade reaction plus in situ oxidative decarboxylation for the transformation of readily available canonical and non‐canonical l ‐α‐amino acids into 2‐substituted 3‐hydroxycarboxylic acid derivatives is described. The biocatalytic cascade consisted of an oxidative deamination of l ‐α‐amino acids by an l ‐α‐amino acid deaminase from Cosenzaea myxofaciens , rendering 2‐oxoacid intermediates, with an ensuing aldol addition reaction to formaldehyde, catalyzed by metal‐dependent ( R )‐ or ( S )‐selective carboligases namely 2‐oxo‐3‐deoxy‐ l ‐rhamnonate aldolase (YfaU) and ketopantoate hydroxymethyltransferase (KPHMT), respectively, furnishing 3‐substituted 4‐hydroxy‐2‐oxoacids. The overall substrate conversion was optimized by balancing biocatalyst loading and amino acid and formaldehyde concentrations, yielding 36–98% aldol adduct formation and 91–98% ee for each enantiomer. Subsequent in situ follow‐up chemistry via hydrogen peroxide‐driven oxidative decarboxylation afforded the corresponding 2‐substituted 3‐hydroxycarboxylic acid derivatives.