Biocatalytic Aldol Addition of Simple Aliphatic Nucleophiles to Hydroxyaldehydes

Asymmetric aldol addition of simple aldehydes and ketones to electrophiles is a cornerstone reaction for the synthesis of unusual sugars and chiral building blocks. We investigated D-fructose-6-phosphate aldolase from E. coli (FSA) D6X variants as catalysts for the aldol additions of linear and cyclic non-functionalized aliphatic ketones or ethanal as nucleophiles to non-phosphorylated hydroxyaldehydes. Thus, addition of propanone, cyclobutanone, cyclopentanone or ethanal to 3-hydroxypropanal or (S)- or (R)-3-hydroxybutanal catalyzed by FSA D6H and D6Q variants furnished rare deoxysugars in 8-77% isolated yields with high stereoselectivity (97:3 dr and >95% ee). © 2018 American Chemical Society.
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 635595 (CarbaZymes), the Ministerio de Economía y Competitividad (MINECO), the Fondo Europeo de Desarrollo Regional (FEDER) (grant CTQ2015-63563-R to P.C. and CTQ2015-64436-P to T.P.), COST action CM1303 Systems Biocatalysis and funding from the Auvergne council.