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Enzymatic and chemoenzymatic 3-step cascades for the synthesis of stereochemically complementary trisubstituted tetrahydroisoquinolines

Erdmann, V; Lichmann, BR; Zhao, J; Simon, RC; Kroutil, W; Ward, JM; Hailes, HC; (2017) Enzymatic and chemoenzymatic 3-step cascades for the synthesis of stereochemically complementary trisubstituted tetrahydroisoquinolines. Angewandte Chemie International Edition , 56 (41) pp. 12503-12507. 10.1002/anie.201705855. Green open access

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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.

Type: Article
Title: Enzymatic and chemoenzymatic 3-step cascades for the synthesis of stereochemically complementary trisubstituted tetrahydroisoquinolines
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/anie.201705855
Publisher version: http://dx.doi.org/10.1002/anie.201705855
Language: English
Additional information: Copyright © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited, and is not used for commercial purposes.
Keywords: asymmetric catalysis; biocatalysis; chemoenzymatic cascades; norcoclaurine synthase; transaminases
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: http://discovery.ucl.ac.uk/id/eprint/1566857
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