Efficient Regioselective Synthesis of Mono-2-O-Sulfonyl-cyclodextrins by the Combination of Sulfonyl Imidazole and Molecular Sieves

Abstract

Cyclodextrins are cyclic oligosaccharides consisting of six or more α-1,4-linked D-glucopyranose units, which possess primary hydroxyl groups at the C-6 positions and secondary hydroxyl groups at the C-2 and C-3 positions. Because cyclodextrins have a hydrophobic and optically active interior, they have been utilized as transporters of hydrophobic molecules and small molecular mimics of enzymes. The chemical modification of cyclodextrins has been investigated in order to improve these characteristics. Sulfonations of the primary or secondary hydroxyl groups of cyclodextrin have been applied for further functionalization of cyclodextrin, and several methods for regioselective sulfonations have been developed. Among these strategies, selective monotosylation of the C-6 hydroxyl group is done relatively easily by reaction of α or β-cyclodextrin and p-toluenesulfonyl chloride in pyridine1,2 or in alkaline aqueous solution.3,4 However, sulfonation of the secondary hydroxyl groups is more difficult and new sulfonation methods must be developed to provide precursors for cyclodextrin analogues such as amino and sulfide analogues. Several strategies for the sulfonation of one C-2 hydroxyl group have been reported. However, because reaction conditions can require specific sulfonation reagent,5 alkaline condition,3-7 strict anhydrous conditions,8,9 or use of protected C-6 hydroxyl groups,10,11 the methodology is not convenient to employ.