Optimised ‘click’ synthesis of glycopolymers with mono/di- and trisaccharides

In this paper we investigate the optimum procedure for the post-polymerisation modification of alkyne-bearing polymer scaffolds with glycosyl azides. We first elaborate the one-pot synthesis of glycosyl azides, in aqueous solution, without the need for protecting groups and in multigram scale. Using these azides, the ligand tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA) was shown to give the fastest kinetics for the ‘click’ reaction at ambient temperature, and was used to prepare homogenous oligosaccharide-modified glycopolymers. The terminal sugars of these oligosaccharides were used to introduce α-linked glucose which is typically synthetically challenging.

[1]  N. Cameron,et al.  A spoonful of sugar: the application of glycopolymers in therapeutics , 2011 .

[2]  Carolyn R. Bertozzi,et al.  Synthesis of Glycopolymers for Microarray Applications via Ligation of Reducing Sugars to a Poly(acryloyl hydrazide) Scaffold , 2010, Journal of the American Chemical Society.

[3]  Matthew I. Gibson,et al.  Postpolymerization modification of poly(pentafluorophenyl methacrylate): Synthesis of a diverse water‐soluble polymer library , 2009 .

[4]  M. Noguchi,et al.  One-step conversion of unprotected sugars to beta-glycosyl azides using 2-chloroimidazolinium salt in aqueous solution. , 2009, Chemical communications.

[5]  P. Neri,et al.  Multivalent galacto-trehaloses: design, synthesis, and biological evaluation under the concept of carbohydrate modules. , 2009, Biomacromolecules.

[6]  N. Cameron,et al.  Inhibition of ice crystal growth by synthetic glycopolymers: implications for the rational design of antifreeze glycoprotein mimics. , 2009, Biomacromolecules.

[7]  Harm-Anton Klok,et al.  Synthesis of functional polymers by post-polymerization modification. , 2009, Angewandte Chemie.

[8]  Patrick Theato,et al.  Synthesis of well‐defined polymeric activated esters , 2008 .

[9]  R. Kane,et al.  The design of polyvalent therapeutics. , 2008, Chemistry.

[10]  A. Imberty,et al.  Glycomimetics and glycodendrimers as high affinity microbial anti-adhesins. , 2008, Chemistry.

[11]  S. Evans,et al.  Site-directed conjugation of "clicked" glycopolymers to form glycoprotein mimics: binding to mammalian lectin and induction of immunological function. , 2007, Journal of the American Chemical Society.

[12]  J. Geng,et al.  Well‐Defined Poly(N‐glycosyl 1,2,3‐triazole) Multivalent Ligands: Design, Synthesis and Lectin Binding Studies , 2007 .

[13]  H. Schlaad,et al.  Thio-click modification of poly [2-(3-butenyl)-2-oxazoline] , 2007 .

[14]  C. Alexander,et al.  Control of bacterial aggregation by thermoresponsive glycopolymers. , 2007, Journal of the American Chemical Society.

[15]  N. Cameron,et al.  Improved synthesis of O-linked, and first synthesis of S- linked, carbohydrate functionalised N-carboxyanhydrides (glycoNCAs). , 2007, Organic & biomolecular chemistry.

[16]  N. Cameron,et al.  Recent advances in the synthesis of well-defined glycopolymers , 2007 .

[17]  Jason E Gestwicki,et al.  Synthetic multivalent ligands as probes of signal transduction. , 2006, Angewandte Chemie.

[18]  Nathan Sharon,et al.  Carbohydrates as future anti-adhesion drugs for infectious diseases. , 2006, Biochimica et biophysica acta.

[19]  V. Ladmiral,et al.  Synthesis of neoglycopolymers by a combination of "click chemistry" and living radical polymerization. , 2006, Journal of the American Chemical Society.

[20]  Benjamin G Davis,et al.  Investigation of the interaction between peanut agglutinin and synthetic glycopolymeric multivalent ligands. , 2005, Organic & biomolecular chemistry.

[21]  K. Sharpless,et al.  Polytriazoles as copper(I)-stabilizing ligands in catalysis. , 2004, Organic letters.

[22]  M. G. Finn,et al.  Click Chemistry: Diverse Chemical Function from a Few Good Reactions. , 2001, Angewandte Chemie.

[23]  Y. Kajihara,et al.  SYNTHESIS OF NEW GLYCOPOLYMERS CONTAINING β-D-MANNOPYRANOSE, AND C-2-SUBSTITUTED β-D-MANNOPYRANOSE RESIDUES AS A NEW CLASS OF INHIBITOR , 2001 .

[24]  Carolyn R. Bertozzi,et al.  Chemical Glycobiology , 2001, Science.

[25]  D. Haddleton,et al.  Atom Transfer Polymerization of Methyl Methacrylate Mediated by Alkylpyridylmethanimine Type Ligands, Copper(I) Bromide, and Alkyl Halides in Hydrocarbon Solution , 1999 .

[26]  T. Uryu,et al.  Synthesis of polymethacrylate derivatives having sulfated maltoheptaose side chains with anti‐HIV activities , 1999 .

[27]  G. Whitesides,et al.  Generation and in Situ Evaluation of Libraries of Poly(acrylic acid) Presenting Sialosides as Side Chains as Polyvalent Inhibitors of Influenza-Mediated Hemagglutination , 1997 .

[28]  L. Kiessling,et al.  Recognition Specificity of Neoglycopolymers Prepared by Ring-Opening Metathesis Polymerization , 1996 .

[29]  G M Whitesides,et al.  Effective inhibitors of hemagglutination by influenza virus synthesized from polymers having active ester groups. Insight into mechanism of inhibition. , 1995, Journal of medicinal chemistry.

[30]  I. Goldstein,et al.  An examination of the topography of the saccharide binding sites of concanavalin A and of the forces involved in complexation. , 1970, Biochemistry.