Synthesis and PEGylation of a novel, per-6-substituted propargyl sulfonamide β-cyclodextrin

Abstract

A novel single isomer, per-6-substituted alkyne-terminated sulfonamide β-cyclodextrin (β-CD) was synthesized, in two steps, from heptakis-2,3-O-dimethyl-6-O-sulfobutyl-β-CD, sodium salt. The intermediate sulfonamide β-CD was then per-6-PEGylated in a third step with azide-terminated polyethylene glycols (N₃-PEG₅-OH and N₃-PEG₄₇-OCH₃) by copper-catalyzed azide-alkyne cycloaddition (CuAAC) The described derivatization strategy is the first to exploit the reactivity of sulfonate functions of sulfobutylether (SBE) anionic cyclodextrins, and results in a water-soluble, single isomer PEG-triazole-sulfonamide β-CD with an extended hydrophobic cavity.