Modern Synthetic Methods in Carbohydrate Chemistry

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.

Auteur
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.

Contenu

Foreword xv

Preface xvii

List of Contributors xix

1 De Novo Approaches to Monosaccharides and Complex Glycans 1
Michael F. Cuccarese, Jiazhen J. Li, and George A. O'Doherty

1.1 Introduction 1

1.2 De Novo Synthesis of Monosaccharides 4

1.3 Iterative Pd-Catalyzed Glycosylation and Bidirectional Postglycosylation 5

1.3.1 Bidirectional Iterative Pd-Catalyzed Glycosylation and Postglycosylation 6

1.3.2 Synthesis of Monosaccharide Aminosugar Library 7

1.4 Synthesis of Monosaccharide Azasugar 9

1.5 Oligosaccharide Synthesis for Medicinal Chemistry 10

1.5.1 Tri- and Tetrasaccharide Library Syntheses of Natural Product 12

1.5.2 Anthrax Tetrasaccharide Synthesis 17

1.6 Conclusion and Outlook 21

1.7 Experimental Section 22

List of Abbreviations 24

Acknowledgments 25

References 25

2 Synthetic Methodologies toward Aldoheptoses and Their Applications to the Synthesis of Biochemical Probes and LPS Fragments 29
Abdellatif Tikad and Stéphane P. Vincent

2.1 Introduction 29

2.2 Methods to Construct the Heptose Skeleton 29

2.2.1 Olefination of Dialdoses Followed by Dihydroxylation 31

2.2.1.1 Olefination at C-5 Position of Pentodialdoses 31

2.2.1.2 Olefination at C-1 Position of Hexoses 33

2.2.1.3 Olefination at C-6 Position of Hexodialdoses 33

2.2.2 Homologation by Nucleophilic Additions 35

2.2.2.1 Elongation at C-6 of Hexoses 35

2.2.2.2 Elongation at C-1 Position of Aldose 41

2.2.3 Heptose de novo synthesis 44

2.3 Synthesis of Heptosylated Oligosaccharides 46

2.3.1 Synthesis of the Core Tetrasaccharide of Neisseria meningitides Lipopolysaccharide 46

2.3.2 Synthesis of a Branched Heptose- and Kdo-Containing Common Tetrasaccharide Core Structure of Haemophilus influenza Lipopolysaccharides 47

2.3.3 Synthesis of the Core Tetrasaccharide of Neisseria gonorrhoeae Lipopolysaccharide 48

2.3.4 The Crich's Stereoselective -Glycosylation Applied to the Synthesis of the Repeating Unit of the Lipopolysaccharide from Plesimonas shigelloides 49

2.3.5 De Novo Approach Applied to the Synthesis of a Bisheptosylated Tetrasaccharide 51

2.4 Synthesis of Heptosides as Biochemical Probes 52

2.4.1 Bacterial Heptose Biosynthetic Pathways 53

2.4.2 Artificial D-Heptosides as Inhibitors of HldE and GmhA 54

2.4.3 Inhibition Studies of Heptosyltransferase WaaC 56

2.5 Conclusions 57

2.6 Experimental Part 58

2.6.1 Typical Synthesis of a D-glycero-Heptoside by Dihydroxylation of a C6C7 Alkene 58

2.6.1.1 Phenyl 1-deoxy-2,3,4-tri-O-benzyl-1-thio-D-glycero--D-mannoheptopyranoside (167) 58

2.6.2 Typical Synthesis of a L-glycero-Heptoside by Addition of Grignard Reagent Followed by a TamaoFleming Oxidation 58

2.6.2.1 Methyl 2,3,4-tri-O-benzyl-7-(phenyldimethyl)silane-7-deoxy-L-glycero-D-manno-heptopyranoside (170) 59

2.6.2.2 Methyl 2,3,4-tri-O-benzyl-L-glycero--D-manno-heptopyranoside (171) 60

List of Abbreviations 60

Acknowledgments 61

References 61

3 Protecting-Group-Free Glycoconjugate Synthesis: Hydrazide and Oxyamine Derivatives in N-Glycoside Formation 67
Yoshiyuki A. Kwase, Melissa Cochran, and Mark Nitz

3.1 Introduction 67

3.2 Glycosyl Hydrazides (1-(Glycosyl)-2-acylhydrazines) 68

3.2.1 Formation, Tautomeric Preference, and Stability of Glycosyl Hydrazides 68

3.2.2 Analytical Applications 70

3.2.3 Hydrazides in Synthesis 73

3.2.4 Biologically Active Glycoconjugates 75

3.2.5 Lectin-Labeling Strategies Using Glycosyl Hydrazides 77

3.2.6 Summary of Glycosyl Hydrazides 79

3.3 O-Alkyl-N-Glycosyl Oxyamines 79

3.3.1 Formation, Configuration, and Stability of O-Alkyl-N-Glycosyloxyamines 79

3.3.2 Uses of O-Alkyl-N-Glycosyl Oxyamines 80

3.4 N,O-Alkyl-N-Glycosyl Oxyamines 80 3.4.1 Uses of N-Alkyl-N-Glycosyloxyamines 83</p&g...