Synthesis of carbohydrate–BODIPY hybrids

Abstract

Abstract Owing to the relevance of fluorescently labeled carbohydrates in the study of biological processes, we have investigated several routes for the preparation of saccharides covalently linked to borondipyrromethene (BODIPY) fluorophores. We have shown that BODIPY dyes can be used as aglycons through synthetic saccharide protocols. In particular, a per-alkylated 8-(2-hydroxy-methylphenyl)-4,4′-dicyano-BODIPY derivative, which withstands glycosylation and protection/deprotection reaction conditions without decomposition, has been used in the stepwise synthesis of two fluorescently labeled trisaccharides. These saccharides displayed high water solubility and a low tendency to (H-)aggregation, a phenomenon that causes loss of photophysical efficiency in BODIPYs. Two additional synthetic strategies toward glyco-BODIPYs have also been described. The first method relies on a Ferrier-type C-glycosylation of the BODIPY core, leading to linker-free carbohydrate–BODIPY hybrids. Secondly, the application of the Nicholas propargylation reaction to 1,3,5,7-tetramethyl BODIPYs provides access to 2,6-dipropargylated BODIPYs that readily undergo CuAAC reactions with azido-containing sugars. From a photophysical standpoint, the BODIPY-labeled saccharides could be used as stable and fluorescent water-soluble chromophores, thereby addressing one of the current challenges in molecular imaging.