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

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...

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Detalles Bibliográficos
Autores: Ford, Grayson J., Swanson, Christopher R., Bradshaw Allen, Ruth T., Marshall, James R., Mattey, Ashley P., Turner, Nicholas J., Clapés Saborit, Pere, Flitsch, Sabine L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/280894
Acceso en línea:http://hdl.handle.net/10261/280894
https://api.elsevier.com/content/abstract/scopus_id/85138221692
Access Level:acceso abierto
Palabra clave:Stereoselective synthesis
Aldolase
Amino-diol
Amino-polyol
Biocatalysis
Enzyme cascades
FSA
IRED
Descripción
Sumario: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.