Palladium‐Catalyzed Oxidation of Glucose in Glycopeptides**

Abstract

Selective modification of carbohydrate residues in glycopeptides is highly relevant as a tool in glycobiology. In particular, oxidation allows for subsequent ligation with a label or handle and 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 applied palladium-catalyzed oxidation for the same purpose. The catalyst, [(neocuproine)PdOAc] 2 OTf 2 , developed for the site-selective oxidation of mono-and oligosacchar-ides on preparative scale, proved suitable 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 function can be used for an oxime-ligation to biotin. A protocol for the analysis of the products using mass spectrometry is also reported.

Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols

“…We propose that steric interactions between the bulky L 3 ligand and glycoside substrates may overcome intrinsic electronic factors that favor oxidation at C3 . The dependence of chemoselectivity on the ligand structure observed here therefore offers an opportunity to obtain rare oxidized glycosides, which can undergo further functionalization to yield valuable carbohydrate products. ,− …”

Site‐Selective Palladium‐catalyzed Oxidation of Unprotected Aminoglycosides and Sugar Phosphates

“…The problems associated with catalyst inhibition can occasionally be overcome by using the palladium catalyst in excess, often in combination with excess ligand. [2,4,7,31] Under these conditions, the catalyst concentration in solution will be sufficient to perform the reaction, even when most of the catalyst forms non-productive complexes with the Lewis basic groups in the substrate (Figure 1D). High catalyst loadings are standard for palladium-mediated cross-coupling reactions on proteins, [7] and have also been used to promote other palladium-catalyzed reactions that suffer from catalyst inhibition.…”

Synthesis of Methylene Tetrahydrofurane‐Fused Carbohydrates

“…As an alternative to the commonly used strategies, the field of regioselective modification of unprotected carbohydrates is growing rapidly [23–25] . In this connection, the groups of Minnaard and Waymouth have shown that the C‐3 hydroxy group in pyranosides can be selectively oxidized with a palladium catalyst to afford the corresponding 3‐ketosaccharide [26–29] . Further modification and derivatization have also been done on these unprotected ketosaccharides [30–32] …”

“…[23][24][25] In this connection, the groups of Minnaard and Waymouth have shown that the C-3 hydroxy group in pyranosides can be selectively oxidized with a palladium catalyst to afford the corresponding 3-ketosaccharide. [26][27][28][29] Further modification and derivatization have also been done on these unprotected ketosaccharides. [30][31][32] Here, we show how the C3-keto functionality in unprotected carbohydrates can be used to introduce an allyl group, which in turn is transformed into a fused methylene-tetrahydrofuran ring (Scheme 1).…”