Approaches to new derivatives of cellulose as designed pharmaceutical excipients

Recently, our group initiated a synthetic program directed at new derivatives of cellulose intended as novel pharmaceutical excipients. With several notable exceptions, the attempted regioselective introduction of chemical functionality into natural cellulose by direct chemical modification will result in heterogeneous products that are difficult to characterize and the preparation of which is insufficiently reproduceable. Approaches to the chemical polymerization of appropriate glucose monomers are available, leading to a degree of polymerization in the order of 100. However, the nature of these processes does not readily lend itself to the preparation of products comprising regularly arranged protecting groups in defined positions. We have chosen a mixed organic chemical-enzyme catalyzed approach based on a procedure of Kobayashi, Shoda, Donnelly and Church. Fluoride derivatives of cellobiose may be polymerized, under catalysis by cellobiose hydrolase, to form cellulose oligosaccharides of different chain lengths. We describe the chemical syntheses of cellobiose fluoride derivatives comprising protecting groups in defined positions of the reducing or nonreducing glucose moieties of cellobiose. Such derivatives may be polymerized to afford cellulose derivatives with protecting groups on alternate glucose units. The processing of these protected cellulose derivatives to afford novel biomimetic polymers will be described.