Chemoenzymatic cascades toward Methylated Tetrahydroprotoberberine and Protoberberine Alkaloids

Roddan, R. and Subrizi, F. and Broomfield, J. and Ward, J.M. and Keep, Nick and Hailes, H.C. (2021) Chemoenzymatic cascades toward Methylated Tetrahydroprotoberberine and Protoberberine Alkaloids. Organic Letters 23 (16), pp. 6342-6347. ISSN 1523-7060.

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Official URL: https://doi.org/10.1021/acs.orglett.1c02110

Abstract

Tetrahydroprotoberberine and protoberberine alkaloids are a group of biologically active natural products with complex molecular scaffolds. Isolation from plants is challenging and stereoselective synthetic routes, particularly of methylated compounds are limited, reducing the potential use of these compounds. In this work, we describe chemoenzymatic cascades toward various 13-methyl-tetrahydroprotoberberbine scaffolds using a stereoselective Pictet-Spenglerase, regioselective catechol O-methyltransferases and selective chemical Pictet-Spengler reactions. All reactions could be performed sequentially, without the workup or purification of any synthetic intermediates. Moreover, the naturally occurring alkaloids have the (+)-configuration and importantly here, a strategy to the (−)-isomers was developed. A methyl group at C-8 was also introduced with some stereocontrol, influenced by the stereochemistry at C-13. Furthermore, a single step reaction was found to convert tetrahydroprotoberberine alkaloids into the analogous protoberberine scaffold, avoiding the use of harsh oxidizing conditions or a selective oxidase. This work provides facile, selective routes toward novel analogues of bioactive alkaloids.

Metadata

Item Type:	Article
School:	Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
Depositing User:	Administrator
Date Deposited:	16 Sep 2021 10:44
Last Modified:	02 Aug 2023 18:12
URI:	https://eprints.bbk.ac.uk/id/eprint/46035

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