Trivalent Heteroglycoclusters as Focal Point Pseudoenantiomers: Synthesis and Preliminary Biological Evaluation

Abstract

We describe the synthesis of the first heteroglycoclusters featuring three distinct carbohydrate ligands. The obtained pair of stereoisomeric glycoclusters were named “focal point enantiomers”, as the configuration of the focal point is the only varying stereogenic element in these molecules. The first pair of such diastereomeric heteroglycoclusters was accessible by an efficient sequence of protection and sequential glycosylation steps utilizing a mannosyl, a N-acetylglucosaminyl, and a galactosyl donor, respectively, which was applied to a prototype azido-functionalized tris(hydroxymethyl)aminomethane (TRIS) scaffold molecule. The stereoisomers could be distinguished based on an X-ray structure of one of the isomeric key intermediates. As previously shown with divalent counterparts, such heterotrivalent cluster glycosides are useful tools for studying the fine-tuning of carbohydrate recognition. The azido functional group at the focal point of the synthetic scaffold molecule was employed in a conjugation reaction with a linker for further immobilization on a gold surface in order to fabricate glyco-SAMs (self-assembled monolayers). A preliminary biological evaluation of the focal point enantiomers was performed in solution using the well-known model lectin Concanavalin A and the important bacterial lectin FimH.