Synthesis of polyrotaxane–glycine conjugates with various degrees of substitution via conjugation with Boc- or Z-glycine and subsequent deprotection

Abstract

Two types of polyrotaxane (PR)–glycine conjugates with different degrees of substitution (DS) were prepared by N,N′-carbonyldiimidazole-mediated esterification. A wide range of DS values were achieved by varying the reaction conditions, including the stoichiometric ratios of protected glycines to hydroxyls, reaction temperatures and reaction times. Varying the stoichiometric ratios gave the broadest DS control. Subsequent deprotection yielded cationic PR derivatives with different DS values. Successful deprotection of Z groups was achieved only by treatment with a trifluoroacetic acid/thioanisole mixture, but was unsuccessful using conventional hydrogenation and treatment with a hydrobromic acid/acetic acid mixture. The DS values of the deprotected derivatives determined by colloidal titration agreed well with those of the protected conjugates determined by 1H nuclear magnetic resonance, suggesting no removal of the pendant glycines during deprotection. The PR–glycine conjugates with higher DS values were soluble in a wide range of organic solvents, and all of the deprotected derivatives were water soluble. Polyrotaxane (PR)-protected glycine conjugates with different levels of degrees of substitutions (DS) were successfully prepared by varying reaction temperature, reaction times and stoicheometric ratios of AA to −OH in PR. Variation of the stoicheometric ratios enabled the widest control of DS values. Z-protecting groups of pendant glycine were removable only by trifluoroacetic acid/thioanisole system.