Chemoenzymatic Approach toward the Synthesis of 3-<i>O</i>-(α/β)-Glucosylated 3-Hydroxy-β-lactams

Abstract

Glycosylation significantly alters the biological and physicochemical properties of small molecules. β-Lactam alcohols comprise eligible substrates for such a transformation based on their distinct relevance in the chemical and medicinal community. In this framework, the unprecedented enzymatic glycosylation of the rigid and highly strained four-membered β-lactam azaheterocycle was studied. For this purpose, <i>cis</i>-3-hydroxy-β-lactams were efficiently prepared in three steps by means of a classical organic synthesis approach, while a biocatalytic step was implemented for the selective formation of the corresponding 3-<i>O</i>-α- and -β-glucosides, hence overcoming the complexities typically encountered in synthetic glycochemistry and contributing to the increasing demand for sustainable processes in the framework of green chemistry. Two carbohydrate-active enzymes were selected based on their broad acceptor specificity and subsequently applied for the α- or β-selective formation of β-lactam-sugar adducts, using sucrose as a glucosyl donor.