Synthesis of chiral α-hydroxy amides by two sequential enzymatic catalyzed reactions

Abstract

Enantiomerically pure alpha-hydroxy amides have been prepared from the corresponding alpha-oxo esters by the use of a double sequence reaction involving in a first step the highly enantioselective Saccharomyces cerevisiae bioreduction and then in a second step, the resulting alpha-hydroxy esters followed a non-enantiospecific lipase catalyzed aminolysis with n-butylamine reaction. In the first non-organic solvent process, the moistened baker's yeast reduced seven alpha-oxo esters with high conversions degree (93% for one substrate and >99% for the others) and high enantioselectivities [>99% for all the substrates except for ketopantoyl lactone, which gave 88% of enantiomeric excess (ee)]. At the same way, the isolated resulting chiral alpha-hydroxy esters were subjected to the second Candida antarctica lipase fraction B (CAL-B) catalyzed aminolysis in dioxane conducting to the corresponding chiral alpha-hydroxy amides with high conversions degree, between 88 and 99%. Both processes were carried out at 28-30 degrees C.