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From the same journal

Enzymatic and Chemoenzymatic Three-Step Cascades for the Synthesis of Stereochemically Complementary Trisubstituted Tetrahydroisoquinolines

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Author(s)

  • Vanessa Erdmann
  • Benjamin R. Lichman
  • Jianxiong Zhao
  • Robert C. Simon
  • Wolfgang Kroutil
  • John M. Ward
  • Helen C. Hailes
  • Dörte Rother

Department/unit(s)

Publication details

JournalAngewandte Chemie - International Edition
DateAccepted/In press - 20 Jul 2017
DateE-pub ahead of print - 27 Sep 2017
DatePublished (current) - 2 Oct 2017
Issue number41
Volume56
Number of pages5
Pages (from-to)12503-12507
Early online date27/09/17
Original languageEnglish

Abstract

Chemoenzymatic and enzymatic cascade reactions enable the synthesis of complex stereocomplementary 1,3,4-trisubstituted tetrahydroisoquinolines (THIQs) with three chiral centers in a step-efficient and selective manner without intermediate purification. The cascade employs inexpensive substrates (3-hydroxybenzaldehyde and pyruvate), and involves a carboligation step, a subsequent transamination, and finally a Pictet–Spengler reaction with a carbonyl cosubstrate. Appropriate selection of the carboligase and transaminase enzymes enabled the biocatalytic formation of (1R,2S)-metaraminol. Subsequent cyclization catalyzed either enzymatically by a norcoclaurine synthase or chemically by phosphate resulted in opposite stereoselectivities in the products at the C1 position, thus providing access to both orientations of the THIQ C1 substituent. This highlights the importance of selecting from both chemo- and biocatalysts for optimal results.

Bibliographical note

© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

    Research areas

  • asymmetric catalysis, biocatalysis, chemoenzymatic cascades, norcoclaurine synthase, transaminases

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