A regio- and stereoselective ω-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines

Research output: Contribution to journalArticle

  • External authors:
  • Elaine O'Reilly
  • Cesar Iglesias
  • Diego Ghislieri
  • Jennifer Hopwood
  • James L. Galman
  • Richard C. Lloyd

Abstract

Biocatalytic approaches to the synthesis of optically pure chiral amines, starting from simple achiral building blocks, are highly desirable because such motifs are present in a wide variety of important natural products and pharmaceutical compounds. Herein, a novel one-pot ω-transaminase (TA)/monoamine oxidase (MAO-N) cascade process for the synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The reactions proceeded with excellent enantio- and diastereoselectivity (>94 % ee; >98 % de) and can be performed on a preparative scale. This methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the transaminase is not affected by the monoamine oxidase, and highlights the potential of this multienzyme cascade for the efficient synthesis of chiral building blocks. Mirror mirror on the wall: A ω-transaminase (ω-TA)/monoamine oxidase (MAO-N) cascade process for the asymmetric synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the TA reaction is not affected by the MAO-N catalyzed step. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographical metadata

Original languageEnglish
Pages (from-to)2447-2450
Number of pages3
JournalAngewandte Chemie - International Edition
Volume53
Issue number9
DOIs
StatePublished - 24 Feb 2014