Preparation of optically pure flurbiprofen via an integrated chemo-enzymatic synthesis pathway

Junichi Enoki, Max Linhorst, Florian Busch, Álvaro Gomez Baraibar, Kenji Miyamoto, Robert Kourist, Carolin Mügge

Research output: Contribution to journalArticle

Abstract

In the synthesis of chiral molecules, the incorporation of enantioselective enzymatic conversions within the synthetic route often presents a useful approach. For the substitution of a chemical step with an enzymatic reaction, however, the complete synthetic route leading to and from this reaction needs to be considered carefully. An integrated approach, taking the possibilities and challenges of both types of conversions into account, can give access to chemo-enzymatic processes with great potential for effective synthesis strategies. We here report on the synthesis of enantiopure flurbiprofen using arylmalonate decarboxylase (AMDase, EC 4.1.1.76) in a chemo-enzymatic approach. Interestingly, practical considerations required shifting the enzymatic step to an earlier position in the synthetic route than previously anticipated. Engineered enzyme variants made it possible to obtain both (R)- and (S)-enantiomers of the target compound in excellent optical purity (>99%ee). The presented results underline that enzymes are most useful when they fit in a synthetic route, and that the optimization of biocatalytic steps and the planning of synthetic routes should be an integrated process.

Original languageEnglish
Pages (from-to)135-142
Number of pages8
JournalMolecular Catalysis
Volume467
DOIs
Publication statusPublished - 2019 Apr 1

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Flurbiprofen
routes
preparation
synthesis
Enzymes
Enantiomers
enzymes
Substitution reactions
enantiomers
Planning
Molecules
planning
purity
substitutes
optimization
molecules

Keywords

  • Asymmetric catalysis
  • Biocatalysis
  • C-C coupling
  • Protecting groups
  • Protein engineering

ASJC Scopus subject areas

  • Catalysis
  • Process Chemistry and Technology
  • Physical and Theoretical Chemistry

Cite this

Preparation of optically pure flurbiprofen via an integrated chemo-enzymatic synthesis pathway. / Enoki, Junichi; Linhorst, Max; Busch, Florian; Baraibar, Álvaro Gomez; Miyamoto, Kenji; Kourist, Robert; Mügge, Carolin.

In: Molecular Catalysis, Vol. 467, 01.04.2019, p. 135-142.

Research output: Contribution to journalArticle

Enoki, Junichi ; Linhorst, Max ; Busch, Florian ; Baraibar, Álvaro Gomez ; Miyamoto, Kenji ; Kourist, Robert ; Mügge, Carolin. / Preparation of optically pure flurbiprofen via an integrated chemo-enzymatic synthesis pathway. In: Molecular Catalysis. 2019 ; Vol. 467. pp. 135-142.
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