Synthesis of 2,5-Disubstituted Pyrrolidine Alkaloids via A One-Pot Cascade Using Transaminase and Reductive Aminase Biocatalysts

Research output: Contribution to journalArticle

  • External authors:
  • Bruna Z. Costa
  • James L. Galman
  • Iustina Slabu
  • Scott P. France
  • Anita J. Marsaioli

Abstract

A multi‐enzymatic cascade process involving transaminases (TAs) and reductive aminases (RedAms) to produce enantiomerically pure 2,5‐disubstituted pyrrolidine alkaloids from their respective 1,4‐diketones is reported. Several TAs were screened and the best results for diketone monoamination were obtained with an R‐selective TA from Mycobacterium chlorophenicum and with an S‐selective TA from Bacillus megaterium. Pyrroline reduction was best performed by a reductive aminase from Ajellomyces dermatitidis (AdRedAm). Finally, a biocatalytic one‐pot cascade was implemented using the aforementioned enzymes and a variety of 2‐methyl‐5‐alkylpyrrolidines were produced with high (>99 %) conversion, diastereomeric and enantiomeric excess values.

Bibliographical metadata

Original languageEnglish
JournalChemCatChem
Early online date23 Aug 2018
DOIs
Publication statusPublished - 2018