A unique overview of the most important protecting group strategies in carbohydrate chemistry
Protecting Groups: Strategies and Applications in Carbohydrate Chemistry provides a detailed account of key strategies and methodologies for the protection of carbohydrates. Divided into two parts, the first focuses on groups that are used best to protect a specific position on a carbohydrate. In the second part, specific carbohydrate residues or compounds are discussed in the context of a specific protecting group strategy used to reach the desired regioisomer. This important book:
-Features chapters on protecting groups at the primary and secondary positions of carbohydrates
-Describes protecting group strategies towards sialic acid derivatives, glycofuranoses, sulfated glycosaminoglycans, and cyclodextrins
-Provides information on automated glycan assembly
-Includes a chapter on the industrial scale synthesis of heparin analogs
Written by a team of leaders in the field, Protecting Groups: Strategies and Applications in Carbohydrate Chemistry is an indispensable guide for academics and industrial researchers interested in carbohydrate and natural product synthesis, pharmaceutical chemistry, and biochemistry.
Table of Contents:
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
About the Author :
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".
Review :
?Protecting Groups: Strategies and Applications in Carbohydrate Chemistry draws together several decades of advances in selectively protecting specific positions of carbohydrates and then takes a fresh look at this area from the perspective of synthetic strategies. (?) Throughout the book, the authors present useful examples of reliable experimental methods for introduction and removal of the most important protecting groups. (?) It is therefore highly suitable for newcomers to the field and for experienced glycochemists or glycobiologists who would like to expand their knowledge of this challenging field. In short, this is a book that should occupy the shelves of every practicing and aspiring carbohydrate chemist.?
Carolyn R. Bertozzi in Angew. Chem. Int. Ed. 2019, 58, 2
