Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

[1]  Larry Norton,et al.  Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[3]  U. Galili.  Interaction of the natural anti-Gal antibody with alpha-galactosyl epitopes: a major obstacle for xenotransplantation in humans. , 1993, Immunology today.

[4]  G. Boons,et al.  Stereoselective 1,2-cis-galactosylation assisted by remote neighboring group participation and solvent effects , 1999 .

[5]  Lisheng Zhu,et al.  Development of a highly α-selective galactopyranosyl donor based on a rational design , 2011 .

[6]  G. Boons,et al.  Chiral auxiliary mediated 1,2-cis glycosylations for the solid supported synthesis of a biologically important branched α-glucan , 2010, Nature chemistry.

[7]  H. Overkleeft,et al.  Automated solid-phase synthesis of β-mannuronic acid alginates. , 2012, Angewandte Chemie.

[8]  Yifan Luo,et al.  Isolation and structural characterization of an immunostimulating polysaccharide from fuzi, Aconitum carmichaeli. , 2006, Carbohydrate research.

[9]  D. Werz,et al.  Modern Synthetic Methods in Carbohydrate Chemistry: From Monosaccharides to Complex Glycoconjugates , 2013 .

[10]  N. Nifantiev,et al.  Is an acyl group at O-3 in glucosyl donors able to control α-stereoselectivity of glycosylation? The role of conformational mobility and the protecting group at O-6. , 2014, Carbohydrate research.

[11]  Kheireddine El-Boubbou,et al.  Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors. , 2007, The Journal of organic chemistry.

[12]  D. Werz,et al.  Comparative bioinformatics analysis of the mammalian and bacterial glycomes , 2011 .

[13]  A. Demchenko.  Handbook of Chemical Glycosylation , 2008 .

[14]  H. Rockette,et al.  From the laboratory to the clinic: the "prevalence effect". , 2003, Academic radiology.

[15]  Biao Yu.  Modern Synthetic Methods in Carbohydrate Chemistry. From Monosaccharides to Complex Glycoconjugates. Edited by Daniel B. Werz and Sebastien Vidal. , 2014 .

[16]  Peter H Seeberger,et al.  Rapid synthesis of a glycosylphosphatidylinositol-based malaria vaccine using automated solid-phase oligosaccharide synthesis. , 2002, Journal of the American Chemical Society.

[17]  G. Sassaki,et al.  An α-Glucan of Pseudallescheria boydii Is Involved in Fungal Phagocytosis and Toll-like Receptor Activation* , 2006, Journal of Biological Chemistry.

[18]  P. Seeberger,et al.  Automated solid-phase synthesis of protected tumor-associated antigen and blood group determinant oligosaccharides. , 2004, Angewandte Chemie.

[19]  S. Danishefsky,et al.  A vision for vaccines built from fully synthetic tumor-associated antigens: from the laboratory to the clinic. , 2013, Journal of the American Chemical Society.

[20]  P. Seeberger,et al.  Streamlined access to conjugation-ready glycans by automated synthesis , 2012 .

[21]  Raymond A. Dwek,et al.  Glycobiology: Toward Understanding the Function of Sugars. , 1996, Chemical reviews.

[22]  Chi-Huey Wong,et al.  Development of Globo-H cancer vaccine. , 2015, Accounts of chemical research.

[23]  G. Boons,et al.  Stereoselective glycosylation reactions with chiral auxiliaries. , 2005, Angewandte Chemie.

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

[25]  K. K. Mong,et al.  Modulating glycosylation with exogenous nucleophiles: an overview. , 2014, Organic & biomolecular chemistry.

[26]  Yukishige Ito,et al.  Recent advances in stereoselective glycosylation through intramolecular aglycon delivery. , 2010, Organic & biomolecular chemistry.

[27]  P. H. Seeberger,et al.  Identification of carbohydrate anomers using ion mobility–mass spectrometry , 2015, Nature.

[28]  A. Demchenko.  Handbook of chemical glycosylation : advances in stereoselectivity and therapeutic relevance , 2008 .

[29]  K. K. Mong,et al.  Dimethylformamide: an unusual glycosylation modulator. , 2011, Angewandte Chemie.

[30]  P. Seeberger.  The logic of automated glycan assembly. , 2015, Accounts of chemical research.

[31]  P. Mahadevan,et al.  An overview , 2007, Journal of Biosciences.

[32]  J. P. Yasomanee,et al.  Effect of remote picolinyl and picoloyl substituents on the stereoselectivity of chemical glycosylation. , 2012, Journal of the American Chemical Society.

[33]  M. Ventura,et al.  The synthesis of compatible solute analogues-solvent effects on selective glycosylation. , 2011, Carbohydrate research.

[34]  J. Bender,et al.  Phase I Trial , 1983 .

[35]  Peter H Seeberger,et al.  Automated polysaccharide synthesis: assembly of a 30mer mannoside. , 2013, Angewandte Chemie.

[36]  D. Werz,et al.  Automated synthesis of the tumor-associated carbohydrate antigens Gb-3 and Globo-H: incorporation of alpha-galactosidic linkages. , 2007, Journal of the American Chemical Society.