Building Block Approach to the Synthesis of a Cucurbit[7]uril Derivative Bearing Sulfonate Functional Groups

Abstract

Low aqueous solubility prevents 40-70% of new pharmaceutical agents from reaching their full potential. The use of molecular containers as solubilizing agents is one solution currently under development. Chapter 1 introduces molecular containers under investigation as drug delivery excipients. Synthetic approaches, properties and important derivatives of cyclodextrins and cucurbiturils are briefly reviewed. Chapter 2 describes the tested hypothesis that the addition of sulfonate functional groups to CB[7] will enhance the aqueous solubility of the CB[7] derivative as compared to CB[7] itself. The building-block approach to obtain a difunctionalized CB[7] derivative by the condensation of glycoluril hexamer (21) and ((¬CH2)4SO3Na)2 glycoluril bis(cyclic ether) (30) is described. The new CB[7] derivative had surprisingly low aqueous solubility (20.2 mM), but very similar molecular recognition properties to those of CB[7]. The CB[7] derivative was investigated for its use as an excipient for drug solubilization and found to have no enhancement compared to CB[7].