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.

Water-soluble co-polyelectrolytes by selective modification of cellulose esters

“…The product 13 C NMR spectrum (Figure 1) provides confirmation that the desired C-6 bromination has cleanly occurred. A newresonanceappears at 37 ppm, consistent with bromo-substituted C-6 (Fox & Edgar, 2012).Based on previous reports (Liu, Liu, Esker &Edgar, 2016;Zhang, Liu & Edgar, 2016), the resonance at ppm is from6-carbonsbearing acetyl groups. Resonances at and 135 ppm indicate that the product contains small proportions ofPh 3 P and its oxide; as inour previous studies, it was difficult to completely remove phosphine impurities from the initial brominated product (Fox & Edgar, 2012;.Satisfyingly, DS(Br) calculated from elemental analysis was 0.49.Since the DS(6-OH)of CA320S was measured as 0.49 by integration of the 6-propionate methyl in the perpropionylated product, C-6 bromination is quantitative.…”

“…Cationic cellulose derivatives have recently received increasing attention, since they are capable of binding electrostatically with anionic biomolecules including nucleic acids and certain proteins to produce therapeutically useful polyelectrolyte complexes (Scranton, Rangarajan & Klier, 1995).Compared to synthetic cationic polymers, cationic cellulose derivatives may in some cases be more attractive candidates for therapeutic uses because they frequently are morebiocompatible and biodegradable, and have low immunogenicity (Samal et al, 2012).Recently wehave prepared cationic derivatives of cellulose and other glucans that possess free 6-OH groupsby reacting trialkylamines with 6-bromo-6deoxyglucans, for example 6-bromo-6-deoxy-2,3-diacetyl-cellulose, which is generated from native cellulose by Furuhata bromination and in situ peracylation (Marks, Fox & Edgar, 2016).However, we found that such nucleophilic bromide displacements by trialkylamines are quite difficult to drive to high reaction conversion, possiblydue to developing chargecharge repulsion in the increasingly cationic product (Liu, Liu, Esker &Edgar, 2016;Marks, Fox & Edgar, 2016;Zhang, Liu & Edgar, 2016).We have also observed thataromatic amines (e.g., pyridine and 1-methylimidazole) are more efficient nucleophiles in such displacement reactions, affording high DS values of the cationic substituents (Liu, Liu, Esker &Edgar, 2016). These cationic cellulose derivatives exhibit surprisingly high thermal stability and good water solubility, and are capable of binding irreversibly to hydrophilic and anionic surfaces.…”

Synthesis of Novel Amino Lactose and Evaluation of Its Antioxidant Property

“…Further evidences showed that, when lactose was drafted to chitosan, these derivatives would cause cell leakage and inhibit the production of enterotoxin . On the other hand, such derivatives benefited from ligands modified onto lactose and showed some other advantages . In order to effectively broaden the applications of new valuable products and materials based on lactose in non‐food industry such as biomedical, cosmetics, and textile areas, lactose can be processed into modified lactose derivatives with chemical methods via the introduction of individual functional moieties to native lactose molecules.…”

Radical Scavenging Activities of Novel Cationic Inulin Derivatives

“…These modifications include esterification, acylation, etherification, methylation, carboxymethylation, and cationic modification [22]. Among them, cationic polysaccharide derivatives have been designed for a number of applications, ranging from anti-bacterial agents to gene delivery vectors and for sewage treatment [30,31,32,33]. It was reported that the antioxidant capacity of chitosan is not only influenced by hydroxyl groups, but also by amidogen [34].…”