Palladium‐Catalyzed Oxidation of Glucose in Glycopeptides

Selective modification of carbohydrate residues in glycopeptides is highly relevant as a tool in glycobiology. Oxidation in particular allows subsequent ligation with a label or handleand can be effectuated enzymatically or chemically. Chemical oxidation of carbohydrate residues in glycopeptides is nearly invariably done using periodate cleavage, leading to aldehydes. In this work we apply palladium-catalyzed oxidation for the same purpose. The catalyst, [(neocuproine)PdOAc]2OTf2, developed for the site-selective oxidation of mono-and oligosaccharides on preparative scale, provedsuitable for the oxidation of glucose residues in a series of glucopeptides. Careful optimization of the reaction conditions is necessary to get acceptable conversions without excessive over-oxidation of amino acid side-chains, in particular threonine. The resulting carbonyl functioncan be used for an oxime-ligation to biotin. A protocol for the analysis of the products using mass spectrometry is presented.