Three-Component Stereoselective Enzymatic Synthesis of Amino-Diols and Amino-Polyols

Autor: Grayson J. Ford, Christopher R. Swanson, Ruth T. Bradshaw Allen, James R. Marshall, Ashley P. Mattey, Nicholas J. Turner, Pere Clapés, Sabine L. Flitsch
Přispěvatelé: European Commission, Ministerio de Ciencia e Innovación (España), European Research Council
Rok vydání: 2022
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 2691-3704
DOI: 10.1021/jacsau.2c00374
Popis: Amino-polyols represent attractive chemical building blocks but can be challenging to synthesize because of the high density of asymmetric functionalities and the need for extensive protecting-group strategies. Here we present a three-component strategy for the stereoselective enzymatic synthesis of amino-diols and amino-polyols using a diverse set of prochiral aldehydes, hydroxy ketones, and amines as starting materials. We were able to combine biocatalytic aldol reactions, using variants of d-fructose-6-phosphate aldolase (FSA), with reductive aminations catalyzed by IRED-259, identified from a metagenomic library. A two-step process, without the need for intermediate isolation, was developed to avoid cross-reactivity of the carbonyl components. Stereoselective formation of the 2R,3R,4R enantiomers of amino-polyols was observed and confirmed by X-ray crystallography.
We kindly acknowledge financial support from the European Research Council (788231-ProgrES-ERC-2017-ADG to S.L.F.; BIO-H-BORROW to N.J.T.). J.R.M. acknowledges the Industrial Biotechnology Innovation Centre (IBioIC) and BBSRC funding through a CASE studentship with Prozomix Ltd. P.C. acknowledges financial support from the project RTI2018-094637-BI00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe” and project PCI2018-092937 MCIN/AEI/10.13039/501100011033 cofunded by the UE under the ERACoBioTech Tralaminol (European Union’s Horizon 2020 research and innovation programme grant agreement no. 722361).
Databáze: OpenAIRE
Externí odkaz: