Chemoenzymatic Approach toward the Synthesis of 3-O-(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, cis-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-O-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.

Stereochemical course of cobalamin-dependent radical SAM methylation by TokK and ThnK

“…A simple doublet was observed at C4 of the azetidinone with J = 6.0 or 2.8 Hz for 14a and 14b, respectively, in accord with Karplus dihedral angle dependence. 38 These key intermediates were separately elaborated to the correspondingly labeled PCPM isotopologues using a strategy similar to that described previously (Scheme 2). 1,24 Briefly, after removal of the benzyl ester by hydrogenolysis to afford 15a and 15b, each carboxylic acid was subjected to an Arndt-Eistert homologation.…”

Sucrose Phosphorylase and Related Enzymes in Glycoside Hydrolase Family 13: Discovery, Application and Engineering

“…The R134A variant was more promiscuous towards large compounds in general. In a different work, the same enzyme was also used for the challenging glucosylation of 3-hydroxy-β-lactams [79].…”

Structural Comparison of a Promiscuous and a Highly Specific Sucrose 6F-Phosphate Phosphorylase

“…For instance, a mutant of TtSPP was rationally designed to achieve high activity towards bulky phenolics such as resveratrol, enabling the quantitative production of a resveratrol glucoside [19]. The same mutant could also be applied for the synthesis of glucosylated 3-hydroxy-β-lactams [20].…”