SYNTHESIS OF SPIN-LABELED C-GLYCOSIDES

Multivalent carbohydrate-lectin interactions have been intensively investigated in the last decades. Still, the molecular binding mechanisms are not well understood. Valuable information can be obtained by X-ray crystallography.^[1] However, methods for studying binding mechanisms in solution are missing. The use of spin-labeled carbohydrates for the investigation of carbohydrate-lectin interactions in solution using distance measurements by EPR spectroscopy has been shown to be a promising approach.^[2] Here, we report the synthesis of spin-labeled C‑glycosides of GlcNAc (1) and lactose (2). One of the key steps of the syntheses was the introduction of the spin-label precursor 3,3,5,5-tetramethylpiperazine-2,6-dione via a Chan-Lam coupling^[3] using the corresponding phenyl boronic acid C-glycosides. Subsequent oxidization to the nitroxide and deprotection gave the spin-labeled sugars. Currently, EPR studies of these interesting compounds are being carried out.

Scheme 1: Synthesis of spin-labeled C-glycosides of GlcNAc 1 and lactose 2.

[1] Schwefel, D., Maierhofer, C., Beck, J. G., Seeberger, S., Diederichs, K., Möller, H. M., Welte, W., Wittmann, V., J. Am. Chem. Soc. 2010, 132, 8704-8719.

[2] Braun, P., Nägele, B., Wittmann, V., Drescher, M., Angew. Chem. Int. Ed. 2011, 50, 8428-8431.

[3] S.Stoller, G. Sicoli, T. Y. Baranova, M. Bennati, U. Diederichsen, Angew. Chem. Int. Ed. 2011, 50, 9743-9746.