Organic Chemistry

Three-component stereoselective enzymatic synthesis of amino diols and amino-polyols

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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 protection 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 (R),(R),(R) enantiomers of amino polyols was observed and confirmed by x-ray crystallography.

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