Pyruvate aldolases from Pfam family PF03328, recently described to be able to use hydroxypyruvic acid as nucleophile substrate, were shown to also catalyse aldol adducts formation from 2-oxobutyric acid. A 1 H NMR-based assay was used to screen 21 aldolases for their activity towards 2oxobutyric acid and to predict their stereoselectivity at position 3 of the aldol adducts. The best biocatalysts were then proved to be strictly (3S)selective. Contrary to known enzymes from this family that are seldom stereoselective at position 4, three aldolases were highlighted as allowing a selective access to (3S,4R) or (3S,4S) aldols. Seven 3-deoxy-3-methylulosonic acids never described before were finally prepared and isolated with good yields and stereoselectivities.
Tertiary alcohols are widely represented in nature and among bioactive molecules. Their importance is attested by the continuous efforts to meet the challenge of their stereoselective synthesis. In this context, we propose an enzymatic approach, involving class II pyruvate aldolases. These enzymes are shown to catalyze selective cross-aldol reactions between pyruvic acid or derivatives as nucleophiles and a series of ketones as electrophiles. This catalytic activity is exemplified by the highly stereoselective preparation of seven branched ketols with good yields. One of them was readily converted into a constrained 4-hydroxyproline analogue in a multi-enzymatic one-pot one-step process.
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