Cyclodextrin-based enzyme models. Part 1. Synthesis of a tosylate and an epoxide derived from heptakis(6-O-tert-butyldimethylsilyl)-β-cyclodextrin and their characterization using 2D NMR techniques. An improved route to cyclodextrins functionalized on the secondary face

Abstract

An improved route for the synthesis of cyclodextrin (CD)-based enzyme models having catalytic groups on the secondary face is presented. An epoxide derived from heptakis(6-O-tert-butyldimethylsilyl)-β-CD was prepared via intermediates that can be purified by conventional flash chromatography on a preparative scale. Reaction of β-cyclodextrin with; tert-butyldimethylsilyl chloride in pyridine gave heptakis(6-O-tert-butyldimethylsilyl)-β-CD (1). Treatment of 1 with N-tosylimidazole and NaOMe in chloroform gave mono(2-O-tosyl) heptakis(6-O-tert-butyldimethylsilyl)-β-CD (2) in 22% yield. The latter was converted smoothly to mono(2^A, 3^A-anhydro) heptakis(6-O-tert-butyldimethylsilyl)-β-CD (3), in which one glucose subunit has been converted to a manno-epoxide, by treatment with KOEt in refluxing ethanol (87% yield). Compounds 1, 2, and 3 were characterized by a variety of one- and two-dimensional NMR techniques. These results open the door to attachment of catalytic groups to the cyclodextrin in a well-defined manner. Nucleophilic attack on the epoxide, followed by removal of the silyl groups, can be used to prepare a wide variety of enzyme model systems. Key words: functionalized cyclodextrins, silylation, 2D NMR, enzyme models.