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

Elaine O'Reilly, Cesar Iglesias, Diego Ghislieri, Jennifer Hopwood, James L. Galman, Richard C. Lloyd, Nicholas J. Turner

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

    Keywords

    • biocatalysis
    • cascade reactions
    • monoamine oxidase
    • pyrrolidines
    • transaminase

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