Efficient Synthesis of Thiolactoside Glycoclusters by Ruthenium-Catalyzed Cycloaddition of Disubstituted Alkynes on Carbohydrate Scaffolds

ALEJANDRO J. CAGNONI; OSCAR VARELA; MARÍA LAURA UHRIG; JOSÉ KOVENSKY

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2012 vol. 2013 p. 972 - 983

1434-193X

Lectin-carbohydrate interactions are responsible for several cellular processes involved in the immune system and the development of certain types of cancer. For the understanding of the cellular responses triggered by these interactions, complex carbohydrates are designed and prepared. In this context, we describe here the synthesis of a family of multivalent glycoclusters based on carbohydrate cores bearing thiolactosides or thiogalactosides as recognition elements with structural valencies ranging from 2 to 8. The synthetic strategy involves as key step the Rutheniumcatalyzed cycloaddition of symmetric disubstituted alkynes bearing two thiosugar units and azide-containing carbohydrate scaffolds. This methodology afforded high-valency glycoconjugates with good to excellent yields. Binding affinities of the synthetic β-thiolactosides for peanut lectin were measured by isothermal titration calorimetry. These titrations revealed micromolar affinities as well as a multivalent effect. A tetravalent glycoconjugate based on a trehalose scaffold displayed the highest binding affinity.