A Concise Route to Water-Soluble 2,6-Disubstituted BODIPY-Carbohydrate Fluorophores by Direct Ferrier-Type C-Glycosylation

Abstract

Novel, linker-free, BODIPY-carbohydrate derivatives containing sugar residues at positions C2 and C6 are efficiently obtained by, hitherto unreported, Ferrier-type C -glycosylation of 8-aryl-1,3,5,7-tetramethyl BODIPYs with commercially available tri- O -acetyl- d -glucal followed by saponification. This transformation, which involves the electrophilic aromatic substitution (S E Ar) of the dipyrrin framework with an allylic oxocarbenium ion, provides easy access to BODIPY-carbohydrate hybrids with excellent photophysical properties and a weaker tendency to aggregate in concentrated water solutions.

meso-Methyl BODIPY Photocages: Mechanisms, Photochemical Properties, and Applications

“…Nevertheless, the BODIPY chromophore is inherently highly hydrophobic, a property that can severely limit the potential concentration and thus utility in water-based solutions. Several strategies have been reported for increasing the water solubility of the BODIPY chromophore, including modifications at the boron center, the 2,6-, 3,5-, or 8-meso position(s) using quaternary ammonium salts, 73,74 sulfonates, 73,75 phosphonates, 76 carbohydrates, 77 amides, 78 zwitterions moieties, 79 or oligo(ethylene glycol) moieties, 73,80 or alternatively, formation of water-soluble nanoparticles via polymer encapsulation or host−guest interactions. 81 In the context of BODIPY as a PPG, only a limited number of these approaches have been explored so far.…”

De Novo Access to BODIPY C-Glycosides as Linker-Free Nonsymmetrical BODIPY-Carbohydrate Conjugates

“…In this context, we have been interested in the emergent field of BODIPY-glycoconjugates, where carbohydrates, one of the four essential types of biomolecules, are covalently linked to BODIPY fluorophores. , In these derivatives, either component may play a relevant role. For example, the carbohydrate moiety has been shown to internalize, solubilize in water, target, and reduce the cytotoxicity of the fluorophore . Conversely, the presence of the fluorophore in BODIPY-carbohydrate conjugates has shown its value in the investigation of carbohydrate-receptor interactions in biological systems with high sensitivity, by way of fluorescently labeled carbohydrates. ,, …”

Chemoselective reaction of methoxyaminomethyl BODIPYs with unprotected carbohydrates: a powerful tool for accessing BODIPY neoglycosides

“…20 The carbohydrate component of BODIPY–carbohydrate conjugates plays an important role since it confers remarkable properties to the BODIPY glycoprobes. Thus, the sugar component provides enhanced solubility in polar solvents (including water), 21 biocompatibility, 22 targeting ability, 23 cell endocytosis, 24 and, in some instances, reduced toxicity 25 to the glyco-fluorophores. 7,8…”

“…7,8 In a broad sense, BODIPY-carbohydrate conjugates can be divided into linker-free or tethered derivatives. Classically, synthetic routes to the former class have been less exploited, 10,21,26 and attention has been mainly devoted to the synthesis of BODIPY-carbohydrate conjugates connected through a "linker". Among the latter, synthetic approaches to tethered BODIPY-carbohydrate hybrids, e.g., 2 (Fig.…”