Glycoconjugates are known to play a crucial rule in many biological events, such as protein structure modulation or cell-cell recognition, and thus became highly attractive targets for drug discovery.[1] For example, tumor-associated glycopeptide antigens (TN) or immunoregulative α-galactosylceramides (KRN 7000) have stimulated an important research interest in recent years. On the other hand, the incorporation of fluorine atoms onto biomolecules or synthetic biologically active molecules has become an intense research field in the past decades, especially for drug development purposes.[2] Despite their interesting biological properties, a major drawback in the use of O-glycosides and O-glycoconjugates for drug development remains the low metabolic stability of the anomeric bond which erodes the bioavailability of carbohydrate-based drugs. It thus appeared interesting to combine the hydrolytic stability of carbohydrate analogues such as C‑glycosides with the unique properties of fluorine to give rise to a new class of glycomimetics.[3] Our group has a long-standing interest in such surrogates and has developed strategies giving access to CF2-glycoside building blocks. Inspired by the success of Richard Franck in the synthesis C‑glycoside analogues of KRN 7000, we investigated the preparation of their CF2 counterparts.[4] For that purpose, we have developed a set of original methodologies allowing access to an α-CF2-galactose building block and to its functionnalization with ceramide side-chains.[5] A first series of GalCer analogues featuring an extra hydroxy group in 1’-position has been prepared and the synthesis of exact analogues is still a work in progress. [1] Wong, C.-H. (Ed.), Carbohydrate-Based Drug Discovery, Wiley-VCH, Weinheim, 2003. [2] Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine, John Wiley & Sons Inc., Hoboken, 2008. [3] Leclerc, E.; Pannecoucke, X.; Ethève-Quelquejeu, M.; Sollogoub, M. Chem. Soc. Rev. 2013, 42, 4270-4283. [4] Franck, R. W.; Tsuji, M. Acc. Chem. Res. 2006, 39, 692-701. [5] Colombel, S.; Van Hijfte, N.; Poisson, T.; Leclerc, E.; Pannecoucke, X. Chem. Eur. J., 2013, 19, 12778-12787.

Synthesis of fluorinated α-galactosylceramide analogs

250th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.