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 0-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 1 H 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.

Amino acid-derivatized slide-ring gels: Chemical crosslinking of polyrotaxane conjugates with different amino acid pendant groups

“…The values for the weight-average molecular weight and polydispersity index, determined using gel-permeation chromatography (GPC) under conditions described in previous studies [19,20], are summarized in Table S1 in the Supporting Information. The average value of the hydroxyl content (HC) values for the PR, which were determined from the 1 H NMR analysis of the PR hydrolyzed using 20% D 2 SO 4 , was 13.89 ± 0.05 and was considered to be nearly constant (see Supporting Information for details).…”

“…Syntheses of the various AA-PR conjugates was performed according to previously reported procedures (Scheme 1) [19,20]. A Typical example using PR and Boc-Ala is briefly described as follows.…”

“…GPC analyses of all the conjugates and colloidal titration for determining the primary amino group content in the deprotected samples were performed in a manner similar to those reported previously [19,20].…”

“…To develop a more versatile method, we prepared the conjugates of PR and glycine (Gly) via an esterification between carboxyl groups in N-protected Gly and the hydroxyl M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 groups in PR, followed by subsequent deprotection. While the Boc groups could be readily removed via conventional treatment using neat trifluoroacetic acid (TFA) [19], the removal of Z groups in the conjugates could not be achieved using common methods, including hydrogenation and hydrobromic acid/acetic acid treatment; it can be achieved only with a TFA/thioanisole system [20]. The variation of the reaction temperature, reaction time, and [AA]/[−OH] stoichiometric ratio enabled control of the degree of substitution (DS) of AA over the range of 5%-60% compared with the PR hydroxyl content [20].…”

“…The authors' research group has been involved in the synthesis of amino acid (AA)-PR conjugates, i.e., PR derivatives with pendant AA moieties [19,20]. Similar conjugates with functional dipeptides were previously synthesized and used for the digested uptake of another model dipeptide [21].…”