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Norcoclaurine Synthase-Mediated Stereoselective Synthesis of 1,1'-Disubstituted, Spiro- and Bis-Tetrahydroisoquinoline Alkaloids

Zhao, J; Méndez-Sánchez, D; Roddan, R; Ward, JM; Hailes, HC; (2021) Norcoclaurine Synthase-Mediated Stereoselective Synthesis of 1,1'-Disubstituted, Spiro- and Bis-Tetrahydroisoquinoline Alkaloids. ACS Catalysis , 11 (1) pp. 131-138. 10.1021/acscatal.0c04704. Green open access

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Abstract

The Pictet–Spenglerase norcoclaurine synthase (NCS) catalyzes the formation of (S)-norcoclaurine, an important intermediate in the biosynthetic pathway of benzylisoquinoline alkaloids. NCS has been used as a biocatalyst with meta-hydroxy phenethylamines and aldehydes for the preparation of single-isomer tetrahydroisoquinoline alkaloids (THIAs). Recently, it was also reported that some ketones can be accepted as substrates, including 4-substituted cyclohexanones and phenyl acetones. Here, we report the use of wild-type NCS and selected variants with aliphatic, cyclic, α-substituted cyclic, heterocyclic, and bicyclic ketones to access challenging non-natural THIAs. Remarkably, fused bicyclic ketones as well as diketones could also be accepted by some of the NCS variants, and in silico modeling was used to provide insights into the rationale for this.

Type: Article
Title: Norcoclaurine Synthase-Mediated Stereoselective Synthesis of 1,1'-Disubstituted, Spiro- and Bis-Tetrahydroisoquinoline Alkaloids
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acscatal.0c04704
Publisher version: https://doi.org/10.1021/acscatal.0c04704
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: biocatalysis, norcoclaurine synthase, Pictet−Spengler, tetrahydroisoquinoline, in silico modeling
UCL classification: UCL
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: https://discovery.ucl.ac.uk/id/eprint/10117768
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