CYCLODEXTRIN-BASED ENZYME MODELS .1. SYNTHESIS OF A TOSYLATE AND AN EPOXIDE DERIVED FROM HEPTAKIS(6-0-TERT-BUTYLDIMETHYLSILYL)-BETA-CYCLODEXTRIN AND THEIR CHARACTERIZATION USING 2D NMR TECHNIQUES - AN IMPROVED ROUTE TO CYCLODEXTRINS FUNCTIONALIZED ON THE SECONDARY FACE

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)-beta-CD was prepared via intermediates that can be purified by conventional flash chromatography on a preparative scale. Reaction of beta-cyclodextrin with tert-butyldimethylsilyl chloride in pyridine gave heptakis(6-O-tert-butyldimethylsilyl)-beta-CD (1). Treatment of 1 with N-tosylimidazole and NaOMe in chloroform gave mono(2-O-tosyl) heptakis(6-O-tert-butyldimethylsilyl)-beta-CD (2) in 22% yield. The latter was converted smoothly to mono(2A, 3A-anhydro) heptakis(6-O-tert-butyldimethylsilyl)-beta-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.