title: Regioselective synthesis of cationic 6-deoxy-6-(N,N,N-trialkylammonio)curdlan derivatives.
abstract: Curdlan, a bioactive β-1,3-glucan, is of intense interest for pharmaceutical and biomedical applications. Cationic derivatives of curdlan and other polysaccharides are especially attractive for their potential to interact in controlled fashion with proteins, among many other possible applications, but relatively few methods exist for their synthesis. Herein we report a regioselective method for preparation of cationic, water-soluble 6-(N,N,N-trialkylammonio)-6-deoxycurdlan salts by reaction of 6-bromo-6-deoxycurdlan and its 2,4-O-diesters with trialkylamines. Dimethyl sulfoxide was identified as the optimal solvent for this nucleophilic displacement to produce cationic curdlan derivatives (80 °C, 24h), providing maximum degree of triethylammonium substitution (DS) of 0.89, exclusively at the C-6 position. 6-Bromo-6-deoxycurdlan was also reacted with heterocyclic amines such as pyridine and imidazole, providing ammonium-substituted curdlan derivatives with substantial DS (0.66 and 0.86, respectively). The new combination of regioselective Furuhata bromination and bromine displacement under optimized conditions with tertiary amines provides access to quaternized curdlan derivatives that possess high, permanent positive charge and are readily water-soluble, properties that indicate potential application promise including for mucoadhesion, permeation enhancement, and delivery of genes and anionic drugs. Regioselectivity and DS of those curdlan ammonium derivatives were quantified by means of (1)H NMR, (13)C NMR and FTIR spectroscopic methods and by elemental analysis.
authors.affiliation: Macromolecules and Interfaces Institute, Virginia Tech, Blacksburg, VA 24061, United States.
authors.forename: Ruoran
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, College of Science, Virginia Tech, Blacksburg, VA 24061, United States.
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Macromolecules and Interfaces Institute, Virginia Tech, Blacksburg, VA 24061, United States; Department of Sustainable Biomaterials, College of Natural Resources and Environment, Virginia Tech, Blacksburg, VA 24061, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Edgar
mesh_terms: D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D047071:beta-Glucans / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D000644:Quaternary Ammonium Compounds; D047071:beta-Glucans; C038459:curdlan; D048271:Chitosan
keywords: Cationic derivatives; Curdlan ammonium; Paracellular permeability enhancer; Regioselectivity; Water-soluble