Chemoenzymatic Cascade Synthesis of Optically Pure Alkanoic Acids by Using Engineered Arylmalonate Decarboxylase Variants

Junichi Enoki, Carolin Mügge, Dirk Tischler, Kenji Miyamoto, Robert Kourist*

*Korrespondierende/r Autor/in für diese Arbeit

Publikation: Beitrag in einer FachzeitschriftArtikel

Abstract

Arylmalonate decarboxylase (AMDase) catalyzes the cofactor-free asymmetric decarboxylation of prochiral arylmalonic acids and produces the corresponding monoacids with rigorous R selectivity. Alteration of catalytic cysteine residues and of the hydrophobic environment in the active site by protein engineering has previously resulted in the generation of variants with opposite enantioselectivity and improved catalytic performance. The substrate spectrum of AMDase allows it to catalyze the asymmetric decarboxylation of small methylvinylmalonic acid derivatives, implying the possibility to produce short-chain 2-methylalkanoic acids with high optical purity after reduction of the nonactivated C=C double bond. Use of diimide as the reductant proved to be a simple strategy to avoid racemization of the stereocenter during reduction. The developed chemoenzymatic sequential cascade with use of R- and S-selective AMDase variants produced optically pure short-chain 2-methylalkanoic acids in moderate to full conversion and gave both enantiomers in excellent enantiopurity (up to 83 % isolated yield and 98 % ee).

Originalspracheenglisch
Seiten (von - bis)5071-5076
Seitenumfang6
FachzeitschriftChemistry - a European Journal
Jahrgang25
Ausgabenummer19
DOIs
PublikationsstatusVeröffentlicht - 1 Apr 2019

ASJC Scopus subject areas

  • !!Catalysis
  • Organische Chemie

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