Modern Synthetic Methods in Carbohydrate Chemistry

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 Göttingen, 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). Sébastien Vidal is Chargé de Recherche at Centre National de la Recherche Scientifique (CNRS) and is responsible of a small research team at ICBMS (Université Claude Bernard Lyon 1, France). In 2000, he has obtained his PhD in organic chemistry from Université 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.

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