Modern Synthetic Methods in Carbohydrate Chemistry: From Monosaccharides to Complex Glycoconjugates

The fields of glycochemistry and glycoscience are rich and varied and where much can be learned from Nature. As Nature is not always able to produce carbohydrates in quantities useful for not only in research but also as therapeutic agents, new ways need to be found to optimize the yield. This book presents an overview of the latest developments in the field of carbohydrates, ranging from de-novo approaches via cyclodextrin chemistry to the synthesis of such highly complex glycoconjugates as glycosphingolipids and GPI anchors. The main emphasis remains on the synthetic aspects making the book an excellent source of information for those already involved in carbohydrate chemistry, as well as for those organic chemists who are beginners in this field. Equally of interest to synthetic chemists, as well as medicinal chemists and biochemists.

Table of Contents:
Foreword Preface DE NOVO APPROACHES TO MONOSACCHARIDES AND COMPLEX GLYCANS Introduction De Novo Synthesis of Monosaccharides Iterative Pd-Catalyzed Glycosylation and Bidirectional Postglycosylation Synthesis of Monosaccharide Azasugar Oligosaccharide Synthesis for Medicinal Chemistry Conclusion and Outlook Experimental Section SYNTHETIC METHODOLOGIES TOWARD ALDOHEPTOSES AND THEIR APPLICATIONS TO THE SYNTHESIS OF BIOCHEMICAL PROBES AND LPS FRAGMENTS Introduction Methods to Construct the Heptose Skeleton Synthesis of Heptosylated Oligosaccharides Synthesis of Heptosides as Biochemical Probes Conclusions Experimental Part PROTECTING-GROUP-FREE GLYCOCONJUGATE SYNTHESIS: HYDRAZIDE AND OXYAMINE DERIVATIVES IN N-GLYCOSIDE FORMATION Introduction Glycosyl Hydrazides (1-(Glycosyl)-2-acylhydrazines) O-Alkyl-N-Glycosyl Oxyamines N,O-Alkyl-N-Glycosyl Oxyamines Concluding Remarks and Unanswered Questions Procedures RECENT DEVELOPMENTS IN THE CONSTRUCTION OF cis-GLYCOSIDIC LINKAGES Introduction Cis-Glycosylation Conclusion STEREOCONTROL OF 1,2-cis-GLYCOSYLATION BY REMOTE O-ACYL PROTECTING GROUPS Introduction Stereodirecting Influence of Acyl Groups at Axial and Equatorial O-3: Opposite Stereoselectivity Proves Anchimeric Assistance Acyl Groups at O-4 in the Galacto Series: Practical Synthesis of Alpha-Glycosides: Complete Stereoselectivity Lack of Stereocontrolling Effect of Acyl Groups at Equatorial O-4 in 4C1 Conformation Effect of Substituents at O-6 Interplay of Stabilized Bicyclic Carbocation and Two H Conformations of Oxocarbenium Ions Conclusion Key Experimental Procedures SYNTHESIS OF AMINOGLYCOSIDES Introduction Amine-Protecting Group Strategies Controlled Degradation of Aminoglycosides Chemoselective Alcohol-Protecting Group Manipulations Strategies for Glycosylation of Aminoglycoside Scaffolds Synthesis of Amphiphilic Aminoglycosides Chemoenzymatic Strategies of the Preparation of Aminoglycoside Analogs Novel Synthetic Strategies of Overcome Resistance to Aminoglycosides Conclusions and Future Perspectives Selected Synthetic Procedures SYNTHESIS OF NATURAL AND NONNATURAL HEPARIN FRAGMENTS: OPTIMIZATIONS AND APPLICATIONS TOWARD MODULATION OF FGF2-MEDIATED FGFR SIGNALING Introduction Total Synthesis of Standard HPN Fragments Total Synthesis of Modified HPN Fragments: Some Synthetic Clues Alternative Synthetic Methods: Means to Build Libraries Biological Evaluation Conclusion and Outlook Experimental Section (General Procedures) LIGHT FLUOROUS-TAG-ASSISTED SYNTHESIS OF OLIGOSACCHARIDES Introduction Fluorous-Protecting Groups and Tags Amenable to Fluorous Solid-Phase Extraction in Carbohydrate Synthesis Light Fluorous-Protecting Groups with Potential Use in Oligosaccharide Synthesis "Cap-Tag" Strategies or Temporary Fluorous-Protecting Group Additions Double-Tagging Carbohydrates with Fluorous-Protecting Groups Other Advantages to Fluorous-Assisted Oligosaccharide Synthesis Conclusions and Outlook Experimental Section ADVANCES IN CYCLODEXTRIN CHEMISTRY Introduction General Reactivity, Per- and Monofunctionalization Capping Reagents for Direct Modification Bulky Reagents for Direct Modifications Selective Deprotections Conclusions and Perpectives Experimental Procedures DESIGN AND SYNTHESIS OF GM1 GLYCOMIMETICS AS CHOLERA TOXIN LIGANDS Introduction Cholera Toxin and Its Specific Membrane Receptor, the GM1 Ganglioside Rational Design of GM1-os Mimetics as Cholera Toxin Inhibitors and Synthesis of First-Generation Ligands Third Generation of GM1 Ganglioside Mimics: Toward Nonhydrolyzable Cholera Toxin Antagonists Conclusions Experimental Section NOVEL APPROACH TO COMPLEX GLYCOSPHINGOLIPIDS Introduction Syntheses of Complex Glycans of Gangliosides Total Syntheses of Complex Gangliosides Conclusion and Outlook Experimental Section CHEMICAL SYNTHESIS OF GPI ANCHORS AND GPI-ANCHORED MOLECUES Introduction Challenges in the Synthesis of GPIs Tools for Synthesis of GPIs Synthesis of GPIs with Linear Glycan Core Synthesis of GPIs with Branched Glycan Core GPI Derivatives for Biological Research Synthesis of GPI-Anchored Peptides and Proteins Conclusions and Outlook Index

About the Author :
Daniel B. Werz is Professor at the Technical University of Braunschweig, Germany. Having obtained his diploma (2000) as well as his Ph.D. (2003) from University of Heidelberg he spent over two years of postdoctoral research with Peter H. Seeberger at ETH Zurich, Switzerland, before starting his independent career at the University of Gottingen, Germany. In spring 2013 he took up his present position as an associate professor in Braunschweig. Prof. Werz has authored and co-authored over 100 scientific publications and has received several scientific fellowships and awards, including the Ruprecht Karls Award of the University of Heidelberg (2004), a Feodor Lynen Fellowship of the Alexander von Humboldt Foundation (2004), the Klaus Grohe Award of the German Chemical Society (2006), the Emmy Noether Fellowship of the German Research Foundation (2007), the GlycoThera Award (2010) and the highly prestigious Dozentenstipendium of the Chemical Industry Fund (2011). Sebastien Vidal is Charge de Recherche at Centre National de la Recherche Scientifique (CNRS) and is responsible of a small research team at ICBMS (Universite Claude Bernard Lyon 1, France). In 2000, he has obtained his PhD in organic chemistry from Universite Montpellier II (France) working on mannose 6-phosphate analogues. He then continued as a postdoctoral fellow in the group of J. Fraser Stoddart at University of California, Los Angeles for three years to design synthetic methodologies for the preparation of glycodendrimers. After another postdoctoral position at the National Renewable Energy Laboratory (NREL, Golden, Colorado, USA) under the guidance of Joseph J. Bozell, he then moved back to France and was appointed as a CNRS fellow in 2004. Dr. Vidal has co-authored over 60 scientific publications devoted to organic and carbohydrate chemistry.