Azide reduction by DTT or thioacetic acid provides access to amino and amido polysaccharides
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Amino and amido polysaccharides include some of the most complex, fascinating natural polymers, due in part to their important biological activities and intriguing biomedical applications. Chemical modification strategies have recently been created in order to access semi-synthetic amino polysaccharides. They typically involve a three-step reaction sequence: introducing a leaving group, azide displacement of that leaving group, and azide reduction to amine or amide. The final azide reduction to amine or amide is a key step, and current reduction methods are limited by chemoselectivity and solubility issues. In this study, we describe an efficient approach to selectively reduce polysaccharide azides to amines, employing 1,4-dithiothreitol (DTT). Azide reduction by DTT has been demonstrated to be effective across a broad range of substrates and under mild conditions. Different polysaccharides (cellulose and curdlan) and organic solvents (DMF, DMAc, and DMSO) were explored, as was chemoselectivity in the presence of functional groups such as esters, with satisfying reduction results in all cases. We further report a new approach to reduce polysaccharide azides directly to acetamides using thioacetic acid, with high conversion, without going through the free amine intermediate. This is new to polysaccharide chemistry and cannot be achieved by any current method. Thorough characterization revealed that the thioacetic acid reduction was chemoselective, with no side reactions observed. Mechanistic study showed that the reaction does not go through an intermediate amine, and appears to be concerted. These azide reductions by DTT and thioacetic acid provide access to amino and amido polysaccharides that will be of great interest for exploring future applications and understanding structure property relationships of amino and amido polysaccharides.
KeywordsAmine Amide DTT Thioacetic acid Azide reduction
We thank the Institute for Critical Technology and Applied Science (ICTAS), the Macromolecules Innovation Institute (MII), and the Virginia Tech Departments of Sustainable Biomaterials and of Chemistry for their financial, facilities, and educational support. We also thank Xiuli Li of Virginia Tech for her help with the 2D-HMBC NMR experiment.
- Daly WH, Lee S (1989) Peptide graft copolymers from soluble aminodeoxycellulose acetate. In: American Chemical Society, Polymer Preprints, Division of Polymer ChemistryGoogle Scholar
- Furuhata K, Koganei K, Chang H-S et al (1992) Dissolution of cellulose in lithium bromide-organic solvent systems and homogeneous bromination of cellulose with N-bromosuccinimide–triphenylphosphine in lithium bromide-N, N-dimethylacetamide. Carbohydr Res 230:165–177. https://doi.org/10.1016/S0008-6215(00)90519-6 CrossRefGoogle Scholar
- Madhunapantula SV, Achur RN, Bhavanandan VP, Gowda DC (2007) The effect of substitution of the N-acetyl groups of N-acetylgalactosamine residues in chondroitin sulfate on its degradation by chondroitinase ABC. Glycoconj J 24:465–473. https://doi.org/10.1007/s10719-007-9039-y CrossRefPubMedGoogle Scholar
- Meng X, Edgar KJ (2016) “Click” reactions in polysaccharide modification. Prog Polym Sci 53:52–85. https://doi.org/10.1016/J.PROGPOLYMSCI.2015.07.006 CrossRefGoogle Scholar