Microwave-Assisted Automated Glycan Assembly

Automated synthesis of DNA, RNA, and peptides provides quickly and reliably important tools for biomedical research. Automated glycan assembly (AGA) is significantly more challenging, as highly branched carbohydrates require strict regioand stereocontrol during synthesis. A new AGA synthesizer enables rapid temperature adjustment from −40 to +100 °C to control glycosylations at low temperature and accelerates capping, protecting group removal, and glycan modifications using elevated temperatures. Thereby, the temporary protecting group portfolio is extended from two to four orthogonal groups that give rise to oligosaccharides with up to four branches. In addition, sulfated glycans and unprotected glycans can be prepared. The new design reduces the typical coupling cycles from 100 to 60 min while expanding the range of accessible glycans. The instrument drastically shortens and generalizes the synthesis of carbohydrates for use in biomedical and material science.

[1]  P. Seeberger,et al.  Automated glycan assembly of Lewis type I and II oligosaccharide antigens† †Electronic supplementary information (ESI) available: Full experimental information, HPLC chromatograms for AGA syntheses, 1H, 13C, COSY and HSQC NMR spectra of all new compounds. See DOI: 10.1039/c9sc00768g , 2019, Chemical science.

[2]  Xinyu Liu,et al.  New insight on 2-naphthylmethyl (NAP) ether as a protecting group in carbohydrate synthesis: a divergent approach towards a high-mannose type oligosaccharide library. , 2011, Chemical communications.

[3]  U. Schepers,et al.  Chemical Synthesis of Glycosaminoglycans. , 2016, Chemical reviews.

[4]  N. Leadbeater,et al.  Microwave energy: a versatile tool for the biosciences. , 2007, Organic & biomolecular chemistry.

[6]  P. Seeberger,et al.  Automated Glycan Assembly: A Perspective , 2019, Journal of the American Chemical Society.

[7]  Ajit Varki,et al.  Biological roles of glycans , 2016, Glycobiology.

[8]  T. Lowary,et al.  Synthesis of unusual N-acylated aminosugar fragments of Mycobacterium marinum lipooligosaccharide IV. , 2015, The Journal of organic chemistry.

[9]  C. Pedersen,et al.  Catalytic Glycosylations in Oligosaccharide Synthesis. , 2018, Chemical reviews.

[10]  P. Nieto,et al.  Microwave-assisted sulfonation of heparin oligosaccharides , 2011 .

[11]  R. Heilbronn,et al.  Automated Glycan Assembly of Oligo-N-Acetyllactosamine and Keratan Sulfate Probes to Study Virus-Glycan Interactions , 2017 .

[12]  P. Seeberger,et al.  Automated synthesis of arabinoxylan-oligosaccharides enables characterization of antibodies that recognize plant cell wall glycans. , 2015, Chemistry.

[13]  M. Delbianco,et al.  Automated glycan assembly as an enabling technology. , 2018, Current opinion in chemical biology.

[14]  M. Caruthers,et al.  Gene synthesis machines: DNA chemistry and its uses. , 1985, Science.

[15]  Peter H. Seeberger,et al.  Automated Solid-Phase Synthesis of Oligosaccharides , 2001, Science.

[16]  T. Lowary,et al.  Synthesis of the Campylobacter jejuni 81-176 Strain Capsular Polysaccharide Repeating Unit Reveals the Absolute Configuration of its O-Methyl Phosphoramidate Motif. , 2018, Angewandte Chemie.

[17]  M. Caruthers,et al.  Novel RNA Synthesis Method Using 5‘-O-Silyl-2‘-O-orthoester Protecting Groups , 1998 .

[18]  T. Lowary,et al.  Synthesis of a Highly Branched Nonasaccharide Chlorella Virus N-Glycan Using a "Counterclockwise" Assembly Approach. , 2020, Organic letters.

[19]  Shin-Ichiro Nishimura,et al.  A new glycosylation method part 3: study of microwave effects at low temperatures to control reaction pathways and reduce byproducts , 2008 .

[20]  Jing Chen,et al.  Revealing the importance of non-thermal effect to strengthen hydrolysis of cellulose by synchronous cooling assisted microwave driving. , 2018, Carbohydrate polymers.

[21]  C. Kappe,et al.  Microwave effects in organic synthesis: myth or reality? , 2013, Angewandte Chemie.

[22]  R. B. Merrifield.  Automated synthesis of peptides. , 1965, Science.

[23]  J. Kovensky,et al.  Microwave-assisted synthesis of long-chain alkyl glucopyranosides. , 2008, Carbohydrate research.

[24]  K. Matyjaszewski,et al.  Automated Synthesis of Well-Defined Polymers and Biohybrids by Atom Transfer Radical Polymerization Using a DNA Synthesizer. , 2017, Angewandte Chemie.

[25]  Chi‐Huey Wong,et al.  ASSEMBLY OF OLIGOSACCHARIDE LIBRARIES WITH A DESIGNED BUILDING BLOCK AND AN EFFICIENT ORTHOGONAL PROTECTION-DEPROTECTION STRATEGY , 1998 .

[26]  Jack J. Chen,et al.  Rapid synthesis of α-ketoamides using microwave irradiation–simultaneous cooling method , 2003 .

[27]  P. Seeberger,et al.  Total Synthesis of Polysaccharides by Automated Glycan Assembly , 2020, Journal of the American Chemical Society.

[28]  G. Stefanidis,et al.  Intensified deracemization via rapid microwave-assisted temperature cycling , 2018 .

[29]  Po-Wei Tsai,et al.  Pharmacologic Application Potentials of Sulfated Polysaccharide from Marine Algae , 2019, Polymers.

[30]  L. Cronin,et al.  Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine , 2020, Nature Chemistry.

[31]  Frank Schuhmacher,et al.  Automated glycan assembly using the Glyconeer 2.1 synthesizer , 2017, Proceedings of the National Academy of Sciences.

[32]  Hejun Li,et al.  Large-scale production of graphene by microwave synthesis and rapid cooling. , 2011, Chemical communications.

[33]  P. Seeberger,et al.  Automated solid-phase synthesis of chondroitin sulfate glycosaminoglycans. , 2013, Angewandte Chemie.

[34]  T. Kawabata,et al.  Perfectly Regioselective and Sequential Protection of Glucopyranosides , 2010 .

[35]  M. Delbianco,et al.  A Capping Step During Automated Glycan Assembly Enables Access to Complex Glycans in High Yield. , 2018, Chemistry.

[36]  F. Compostella,et al.  Synthesis of sulfated galactocerebrosides from an orthogonal beta-D-galactosylceramide scaffold for the study of CD1-antigen interactions. , 2006, Chemistry.

[37]  K. Ágoston,et al.  A new set of orthogonal protecting groups on a monosaccharide scaffold , 2015 .

[38]  J. Westman,et al.  RAPID CARBOHYDRATE PROTECTING GROUP MANIPULATIONS ASSISTED BY MICROWAVE DIELECTRIC HEATING , 2001 .

[39]  K. Polychronopoulou,et al.  Tuning the activity of Cu-containing rare earth oxide catalysts for CO oxidation reaction: Cooling while heating paradigm in microwave-assisted synthesis , 2018, Materials Research Bulletin.