Regioselective Bromination of the Dextran Nonreducing End Creates a Pathway to Dextran-Based Block Copolymers

Abstract

Preparation of polysaccharide-based block copolymers with linear architectures is an important goal, opening up clear application potential and requiring significant advances in polysaccharide regio-and chemoselectivity. Herein we report a simple approach to prepare dextran-based block copolymers. Reaction with N-bromosuccinimide (NBS)/triphenyl phosphine (PPh 3 ) regioselectively brominates the sole primary alcohol of linear, unbranched dextran at C-6 of the nonreducing end monosaccharide. The resulting dextran, monofunctionalized with a terminal C-6 bromide, was coupled with various amine terminated polymers to prepare block copolymers, including dextran-b-poly(ethylene glycol), dextran-b-polystyrene, and dextran-b-poly(N-isopropylacrylamide). These renewable-based block copolymers, prepared in two selective, high-yielding steps from native linear dextran, exhibit various interesting properties. Dextran-b-poly(N-isopropylacrylamide) undergoes thermally induced micellization as revealed by dynamic light scattering (DLS), forming micelles upon exceeding 33 °C. We also observed microphase separation in dextran-bpolystyrene by using small-angle X-ray scattering (SAXS). Overall, this methodology provides a new, highly chemo-and regioselective, versatile route to diverse dextran-based block copolymers with useful properties, enabling drug delivery, compatibilization, and other applications.

2,5-Anhydro-d-Mannose End-Functionalized Chitin Oligomers Activated by Dioxyamines or Dihydrazides as Precursors of Diblock Oligosaccharides

“…Dext m refers to dextran oligomers with m residues. Dextran is a neutral and flexible polysaccharide composed of d -glucose residues linked by α-1,6-linkages, with some short branches. , The diblocks were purified by gel filtration chromatography (GFC) and characterized by NMR. The outcome of the study includes kinetic and structural data for each conjugation step as well as protocols for preparing activated oligosaccharides and pure diblock polysaccharides, the latter forming a basis for future structure–function studies.…”

Regioselective synthesis of polysaccharide–amino acid ester conjugates

“…Cellulose acetate (CA320S, Eastman Chemical, DS(Ac) 1.78, DS(6-OH) 0.49, Mw = 47.6 kDa ) and dextran from Leuconostoc mesenteroides (Sigma-Aldrich, M n 10,100 g/mol, determined by aqueous SEC (Chen et al, 2020)) were dried under vacuum at 50 • C overnight before use. Lithium bromide (Fisher) was dried under vacuum at 130 • C overnight before use.…”

“…Chen recently reported a method for brominating the available 6-OH at the non-reducing terminus of linear dextran, using Ph 3 P/NBS in DMSO (Chen et al, 2020). However, reactions of NBS in DMSO can be plagued by side reactions, for example rapidly affording a brominecontaining sulfur cation, consuming NBS (Wu et al, 2020).…”

“…Furuhata et al reported a method for regioselective bromination of cellulose using N-bromosuccinimide (NBS) and triphenylphosphine (Ph 3 P) in the dimethylacetamide (DMAc) and LiBr solvent system (Furuhata et al, 1992). The Edgar group has exploited this regioselective bromination to modify C6 polysaccharide hydroxyls and generate useful materials, including those from microcrystalline cellulose (in DMAc/LiBr) (Fox & Edgar, 2012), cellulose esters (in DMAc) , curdlan (in DMAc/LiBr) (Zhang et al, 2017), pullulan (in N, N-dimethylformamide (DMF)/LiBr) (Pereira & Edgar, 2014), and dextran (in dimethyl sulfoxide (DMSO)) (Chen et al, 2020). Recently, the Edgar group reported regioselective chlorination of polysaccharides at the primary hydroxyl groups using methanesulfonyl chloride in DMF; this method employs less expensive reagents and has the significant benefit that it does not generate triphenylphosphine oxide, which can be difficult to remove quantitatively from the polysaccharide product .…”

Functionalisation of the non-reducing end of chitin by selective periodate oxidation: A new approach to form complex block polysaccharides and water-soluble chitin-based block polymers

“…Preparation of more complex block polysaccharides, such as linear ABA or ABC triblock copolymers, requires reactions at the non-reducing end (NRE) of the B block and only a few polysaccharide specific methods for functionalisation of the NRE have been published. However, NRE reactivity has been demonstrated for dextran 3 and lyase degraded heparin 4 after intermediate functionalisation steps.…”