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

ABSTRACT: 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.

SUBMITTER: Ford GJ

PROVIDER: S-EPMC9597598 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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

Ford Grayson J GJ Swanson Christopher R CR Bradshaw Allen Ruth T RT Marshall James R JR Mattey Ashley P AP Turner Nicholas J NJ Clapés Pere P Flitsch Sabine L SL

JACS Au 20220905 10

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- ...[more]

PMID: 36311836

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