Protecting Groups: Strategies and Applications in Carbohydrate Chemistry

Sébastien Vidal, PhD, holds a CNRS position at the University of Lyon, France. His main area of research is the design of glycoclusters for anti-adhesive strategy against bacterial infections and enzyme inhibitors targeting glycogen phosphorylase with applications in type-2 diabetes. In 2014, he was given the young investigator award "Prix du Groupe Français des Glycosciences".

Foreword xvii

Preface xix

1 Protecting Group Strategies in Carbohydrate Chemistry 1
Anne G. Volbeda, Gijs A. van der Marel, and Jeroen D. C. Codée

1.1 Discriminating Different Functionalities on a Carbohydrate Ring 1

1.2 Strategies for an (Oligo)saccharide Synthesis Campaign 5

1.3 Reactivity and Stereochemistry 7

1.4 Protecting Groups in Automated Synthesis 14

1.5 Summary and Outlook 20

Abbreviations 23

References 24

2 Protecting Groups at the Primary Position of Carbohydrates 29
Marion Donnier‐Maréchal, Sébastien Vidal, and Michele Fiore

2.1 Introduction 29

2.2 Selective Primary Hydroxyl Group Protection 30

2.3 Selective Primary Hydroxyl Group Deprotection 45

2.4 Regioselective Transformations at the Primary Position 53

2.5 Summary and Conclusions 59

2.6 Experimental Section 59

Abbreviations 60

References 61

3 Protecting Groups at the Secondary Positions of Carbohydrates 69
Sébastien Vidal and Peter G. Goekjian

3.1 Introduction 69

3.2 The Major Protecting Group Motifs 72

3.3 Conclusion 95

3.4 Experimental Section 95

Abbreviations 96

References 97

4 Regioselective Protection at the Secondary Positions of Carbohydrates with Acyclic Protecting Groups 109
Peter G. Goekjian and Sébastien Vidal

4.1 Introduction 109

4.2 Regioselective Protections at the 2‐Position 110

4.3 Regioselective Protections at the 3‐Position 122

4.4 Regioselective Protections at the 4‐Position 130

4.5 Regioselective bis‐Protection of the 2,6‐, 3,6‐, and 4,6‐Positions of Hexopyranoside Tetraols 130

4.6 Regioselective Mono‐deprotection of Peracetyl and Perbenzyl Monosaccharides 134

4.7 Summary and Conclusions 135

4.8 Experimental Section 136

Abbreviations 137

References 138

5 Protecting Groups at the Anomeric Position of Carbohydrates 145
Chadamas Sakonsinsiri and W. Bruce Turnbull

5.1 Introduction 145

5.2 O‐alkyl and O‐aryl Glycosides 146

5.3 Glycosyl Esters 151

5.4 Cyclic Acetals, Ketals, and Orthoesters 155

5.5 Silyl Ethers 157

5.6 S‐glycosyl and N‐glycosyl Derivatives 158

5.7 Concluding Remarks 162

5.8 Example Experimental Procedures 164

Abbreviations 165

References 166

6 N‐protecting Groups for 2‐Amino‐2‐deoxy‐glycosides 169
Sébastien Vidal

6.1 Introduction 169

6.2 N‐acyl‐based Protecting Groups 171

6.3 Imido‐based Protecting Groups 175

6.4 Carbamate‐based Protecting Groups 179

6.5 Imine‐ or Enamine‐based Protecting Groups 185

6.6 2‐Deoxy‐2‐azido Derivatives as a Protecting Group 187

6.7 From Glycals to 2‐Azido Intermediates 188

6.8 From Glycals to 2‐Sulfonamido Intermediates 190

6.9 Summary and Conclusions 191

6.10 Experimental Section 191

Abbreviations 192

References 193

7 One‐pot Multistep Regioselective Protection of Carbohydrates Catalyzed by Acids 201
Jean‐Marie Beau, Yann Bourdreux, Guillaume Despras, Alexandra Gouasmat, Géraldine San Jose, Dominique Urban, and Boris Vauzeilles

7.1 Introduction 201

7.2 Examples of Early Developments of the One‐pot Multistep Regioselective Hydroxyl Protection of Carbohydrates 202

7.3 One‐pot Multistep Methods from Silylated Substrates 204

7.4 One‐pot Multistep Methods Catalyzed by Copper Triflate on Unprotected Sugars 216

7.5 Other One‐pot Multistep Methods Catalyzed by Acids 216

7.6 Conclusions and Outlook 220

7.7 Experimental Procedures 220

Acknowledgments 221

Abbreviations 222

References 222

8 Acyl Migrations in Carbohydrate Chemistry 227
Filip S. Ekholm and Reko Leino

8.1 Introduction 227

8.2 Mechanism and Migration Kinetics 228

8.3 Acyl Group Migration – Synthetic Applications 230

8.4 Summary and Conclusions 238

8.5 Selected Experimental Procedures 239

Abbreviations 239

References 240

9 De Novo Asymmetric Synthesis of Oligosaccharides Using Atom‐less Protecting Groups 243
Debarpita Ray and George A. O’Doherty

9.1 Introduction 243

9.2 Atom‐less Protecting Groups 244

9.3 De Novo Approach to Carbohydrates 244

9.4 O’Doherty Approach to Carbohydrates 246

9.5 Conclusion 273

9.6 Experimentals [3] 273

Abbreviations 278

References 279

10 Protecting Group Strategies for Sialic Acid Derivatives 283
Harsha Amarasekara, Szymon Buda, Appi R. Mandhapati, and David Crich

10.1 Introduction 283

10.2 Protection of the Carboxylate Group 283

10.3 Protection of Amine Function 289

10.4 Selective Protection of Alcohols 294

10.5 Access to Protected Sialic Acid Derivatives by Total Synthesis 301

10.6 Access to Protected Sialic Acid Derivatives by Chemoenzymatic Synthesis 301

10.7 Preparation of Methyl (methyl 5‐acetamido‐3,5‐dideoxy‐dglycero‐β‐d‐galacto‐non‐2‐ulopyranosid)onate [20, 22, 104] 301

Abbreviations 302

References 302

11 Strategies Toward Protection of 1,2‐ and 1,3‐Diols in Carbohydrate Chemistry 307
Marie Schuler and Arnaud Tatibouët

11.1 Introduction 307

11.2 Protection as Cyclic Acetals 307

11.3 Protection as Orthoesters 320

11.4 Silylene Acetals as Protecting Groups 324

11.5 Cyclic Carbonate 327

11.6 Summary and Conclusions 329

11.7 Experimental Part: Procedure for Regioselective and Reductive Benzylidene Opening Synthesis of Methyl 2,3,4‐Tri‐O‐benzyl‐α‐d‐glucopyranoside 329

Abbreviations 329

References 330

12 Protecting Group Strategies Toward Glycofuranoses 337
Vincent Ferrières, Laurent Legentil, and Loïc Lemiègre

12.1 Introduction 337

12.2 What About Chemistry Without Protecting Groups? 338

12.3 Protecting Group Interconversion 353

12.4 Multistep Synthesis of Some Furanosyl‐containing Glycosides and Conjugates 358

12.5 The Striking Ring Contraction Strategy 362

12.6 Conclusion Strategy for Synthesizing 4‐Amino‐4‐deoxy and 4‐Deoxy‐4‐thio‐aldose Derivatives 364

Abbreviations 364

References 366

13 Cyclodextrin Chemistry via Selective Protecting Group Manipulations 371
Juan M. Benito and José M. García Fernández

13.1 Introduction 371

13.2 Per‐O‐protection of Cyclodextrins 373

13.3 Face‐selective Differentiation: Primary vs Secondary Hydroxyl Protection 374

13.4 Single Hydroxyl Protection Strategies 379

13.5 Concerted Protection of Hydroxyl Sets (Pairs or Triads) 381

13.6 Regioselective Deprotection of Symmetric Cyclodextrins 384

13.7 Summary and Conclusions 388

13.8 Experimental Procedures 388

Abbreviations 389

References 390

14 Protecting Group Strategies Toward Sulfated Glycosaminoglycans 395
Hélène Ledru, Pascal Matton, Jean‐Maurice Mallet, and Chrystel Lopin‐Bon

14.1 Introduction 395

14.2 O‐ and N‐sulfation in Glycosaminoglycan Glycosaminoglycans Synthesis 397

14.3 Protecting Group Strategies for the Synthesis of Sulfated Oligosaccharides of the Proteoglycans Linkage Region 397

14.4 Protecting Group Strategy for the Synthesis of Chondroitin Sulfate 403

14.5 Protecting Groups in Heparin and HS Synthesis 415

14.6 Summary and Conclusions 419

14.7 Experimental Part: Procedure for Regioselective 6‐O‐benzoylation Followed by 4‐Sulfation, an Example of the Synthesis of Disaccharide 31 [18] 419

Abbreviations 420

References 421

15 Applications of Fluorous and Ionic Liquid Tags in Oligosaccharide Synthesis 423
Imke Sittel and M. Carmen Galan

15.1 Introduction 423

15.2 Fluorous Supports 424

15.3 Ionic Liquid Supports 436

15.4 Conclusions 447

Abbreviations 447

References 448

16 Orthogonally Protected Building Blocks for Automated Glycan Assembly 451
Fabian Pfrengle and Peter H. Seeberger

16.1 Introduction 451

16.2 Protecting Groups 452

16.3 General Strategy for the Design of Orthogonally Protected Building Blocks 460

16.4 “Approved Building Blocks” for Automated Glycan Assembly 461

16.5 Solid‐phase Syntheses of Mammalian, Microbial, and Plant Oligosaccharides 464

16.6 Chances, Challenges, and Commercialization of Automated Glycan Assembly 467

Abbreviations 469

References 470

17 Kilogram‐scale Production of Synthetic Heparin Analogs: Some Chemical Considerations 473
Patrick Trouilleux, Pierre Potier, and Pierre‐Alexandre Driguez

17.1 Introduction 473

17.2 Kilogram Synthesis of Heparin Building Blocks 474

17.3 Experimental Section 487

17.4 Summary and Conclusions 489

Abbreviations 489

References 490

Index 493

The New copy of this book will include any supplemental materials advertised. Please check the title of the book to determine if it should include any access cards, study guides, lab manuals, CDs, etc.

The Used, Rental and eBook copies of this book are not guaranteed to include any supplemental materials. Typically, only the book itself is included. This is true even if the title states it includes any access cards, study guides, lab manuals, CDs, etc.