Nonaqueous synthesis of a selectively modified, highly anionic sulfopropyl ether derivative of cyclomaltoheptaose (β-cyclodextrin) in the presence of 18-crown-6

A highly anionic cyclomaltooligosaccharide (cyclodextrin, CD) derivative containing sulfopropyl functional groups on the primary face of the CD was synthesized. Heptakis(2,3-di-O-methyl)cyclomaltoheptaose [heptakis(2,3-di-O-methyl)-beta-cyclodextrin] was reacted with 1,3-propane sultone and potassium hydride (KH) in anhydrous tetrahydrofuran in the presence of 18-crown-6 to yield highly substituted potassium heptakis(2,3-di-O-methyl-6-O-sulfopropyl)cyclomaltoheptaose [heptakis(KSPDM)-beta-CD] with an average degree of substitution (DSCE) of 6.9 as determined by inverse detection capillary electrophoresis (CE). The principal species in the product is the fully substituted heptakis(KSPDM)-beta-CD. Complete NMR assignments of the hydrogen and carbon atoms are made using a combination of gCOSY and gHSQC. In the absence of 18-crown-6, the reaction generates a mixture of multiply charged derivatives with average DSCE of 4.1. The possible roles of the crown ether in the reaction are discussed. The ROESY NMR spectrum of the inclusion complex that forms between heptakis(KSPDM)-beta-CD and 2-naphthoic acid in D2O reveals that 2-naphthoic acid inserts with the carboxyl group toward the derivatized primary rim of the cyclodextrin. (c) 2005 Elsevier Ltd. All rights reserved.