Enzymatic enantioselective aldol reactions of isatin derivatives with cyclic ketones under solvent-free conditions

Nuclease p1 from Penicillium citrinum was observed to directly catalyze the asymmetric aldol reactions between isatin derivatives and cyclic ketones with high isolated yields (up to 95%) and moderate to good stereoselectivity (dr up to >99/1, ee up to 82%). A series of reaction conditions were investigated in detail, and the addition of deionized water had a big influence upon the enzyme activity. This case of biocatalytic promiscuity not only widens the applicability of nuclease p1 to new chemical transformation in organic synthesis, but also provides a potentially valuable method to construct pharmaceutically active compounds in medicinal chemistry. (C) 2014 Elsevier Masson SAS. All rights