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 xviiPreface xix1 Protecting Group Strategies in Carbohydrate Chemistry 1Anne G. Volbeda, Gijs A. van der Marel, and Jeroen D. C. Codée1.1 Discriminating Different Functionalities on a Carbohydrate Ring 11.2 Strategies for an (Oligo)saccharide Synthesis Campaign 51.3 Reactivity and Stereochemistry 71.4 Protecting Groups in Automated Synthesis 141.5 Summary and Outlook 20Abbreviations 23References 242 Protecting Groups at the Primary Position of Carbohydrates 29Marion Donnier‐Maréchal, Sébastien Vidal, and Michele Fiore2.1 Introduction 292.2 Selective Primary Hydroxyl Group Protection 302.3 Selective Primary Hydroxyl Group Deprotection 452.4 Regioselective Transformations at the Primary Position 532.5 Summary and Conclusions 592.6 Experimental Section 59Abbreviations 60References 613 Protecting Groups at the Secondary Positions of Carbohydrates 69Sébastien Vidal and Peter G. Goekjian3.1 Introduction 693.2 The Major Protecting Group Motifs 723.3 Conclusion 953.4 Experimental Section 95Abbreviations 96References 974 Regioselective Protection at the Secondary Positions of Carbohydrates with Acyclic Protecting Groups 109Peter G. Goekjian and Sébastien Vidal4.1 Introduction 1094.2 Regioselective Protections at the 2‐Position 1104.3 Regioselective Protections at the 3‐Position 1224.4 Regioselective Protections at the 4‐Position 1304.5 Regioselective bis‐Protection of the 2,6‐, 3,6‐, and 4,6‐Positions of Hexopyranoside Tetraols 1304.6 Regioselective Mono‐deprotection of Peracetyl and Perbenzyl Monosaccharides 1344.7 Summary and Conclusions 1354.8 Experimental Section 136Abbreviations 137References 1385 Protecting Groups at the Anomeric Position of Carbohydrates 145Chadamas Sakonsinsiri and W. Bruce Turnbull5.1 Introduction 1455.2 O‐alkyl and O‐aryl Glycosides 1465.3 Glycosyl Esters 1515.4 Cyclic Acetals, Ketals, and Orthoesters 1555.5 Silyl Ethers 1575.6 S‐glycosyl and N‐glycosyl Derivatives 1585.7 Concluding Remarks 1625.8 Example Experimental Procedures 164Abbreviations 165References 1666 N‐protecting Groups for 2‐Amino‐2‐deoxy‐glycosides 169Sébastien Vidal6.1 Introduction 1696.2 N‐acyl‐based Protecting Groups 1716.3 Imido‐based Protecting Groups 1756.4 Carbamate‐based Protecting Groups 1796.5 Imine‐ or Enamine‐based Protecting Groups 1856.6 2‐Deoxy‐2‐azido Derivatives as a Protecting Group 1876.7 From Glycals to 2‐Azido Intermediates 1886.8 From Glycals to 2‐Sulfonamido Intermediates 1906.9 Summary and Conclusions 1916.10 Experimental Section 191Abbreviations 192References 1937 One‐pot Multistep Regioselective Protection of Carbohydrates Catalyzed by Acids 201Jean‐Marie Beau, Yann Bourdreux, Guillaume Despras, Alexandra Gouasmat, Géraldine San Jose, Dominique Urban, and Boris Vauzeilles7.1 Introduction 2017.2 Examples of Early Developments of the One‐pot Multistep Regioselective Hydroxyl Protection of Carbohydrates 2027.3 One‐pot Multistep Methods from Silylated Substrates 2047.4 One‐pot Multistep Methods Catalyzed by Copper Triflate on Unprotected Sugars 2167.5 Other One‐pot Multistep Methods Catalyzed by Acids 2167.6 Conclusions and Outlook 2207.7 Experimental Procedures 220Acknowledgments 221Abbreviations 222References 2228 Acyl Migrations in Carbohydrate Chemistry 227Filip S. Ekholm and Reko Leino8.1 Introduction 2278.2 Mechanism and Migration Kinetics 2288.3 Acyl Group Migration – Synthetic Applications 2308.4 Summary and Conclusions 2388.5 Selected Experimental Procedures 239Abbreviations 239References 2409 De Novo Asymmetric Synthesis of Oligosaccharides Using Atom‐less Protecting Groups 243Debarpita Ray and George A. O’Doherty9.1 Introduction 2439.2 Atom‐less Protecting Groups 2449.3 De Novo Approach to Carbohydrates 2449.4 O’Doherty Approach to Carbohydrates 2469.5 Conclusion 2739.6 Experimentals [3] 273Abbreviations 278References 27910 Protecting Group Strategies for Sialic Acid Derivatives 283Harsha Amarasekara, Szymon Buda, Appi R. Mandhapati, and David Crich10.1 Introduction 28310.2 Protection of the Carboxylate Group 28310.3 Protection of Amine Function 28910.4 Selective Protection of Alcohols 29410.5 Access to Protected Sialic Acid Derivatives by Total Synthesis 30110.6 Access to Protected Sialic Acid Derivatives by Chemoenzymatic Synthesis 30110.7 Preparation of Methyl (methyl 5‐acetamido‐3,5‐dideoxy‐dglycero‐β‐d‐galacto‐non‐2‐ulopyranosid)onate [20, 22, 104] 301Abbreviations 302References 30211 Strategies Toward Protection of 1,2‐ and 1,3‐Diols in Carbohydrate Chemistry 307Marie Schuler and Arnaud Tatibouët11.1 Introduction 30711.2 Protection as Cyclic Acetals 30711.3 Protection as Orthoesters 32011.4 Silylene Acetals as Protecting Groups 32411.5 Cyclic Carbonate 32711.6 Summary and Conclusions 32911.7 Experimental Part: Procedure for Regioselective and Reductive Benzylidene Opening Synthesis of Methyl 2,3,4‐Tri‐O‐benzyl‐α‐d‐glucopyranoside 329Abbreviations 329References 33012 Protecting Group Strategies Toward Glycofuranoses 337Vincent Ferrières, Laurent Legentil, and Loïc Lemiègre12.1 Introduction 33712.2 What About Chemistry Without Protecting Groups? 33812.3 Protecting Group Interconversion 35312.4 Multistep Synthesis of Some Furanosyl‐containing Glycosides and Conjugates 35812.5 The Striking Ring Contraction Strategy 36212.6 Conclusion Strategy for Synthesizing 4‐Amino‐4‐deoxy and 4‐Deoxy‐4‐thio‐aldose Derivatives 364Abbreviations 364References 36613 Cyclodextrin Chemistry via Selective Protecting Group Manipulations 371Juan M. Benito and José M. García Fernández13.1 Introduction 37113.2 Per‐O‐protection of Cyclodextrins 37313.3 Face‐selective Differentiation: Primary vs Secondary Hydroxyl Protection 37413.4 Single Hydroxyl Protection Strategies 37913.5 Concerted Protection of Hydroxyl Sets (Pairs or Triads) 38113.6 Regioselective Deprotection of Symmetric Cyclodextrins 38413.7 Summary and Conclusions 38813.8 Experimental Procedures 388Abbreviations 389References 39014 Protecting Group Strategies Toward Sulfated Glycosaminoglycans 395Hélène Ledru, Pascal Matton, Jean‐Maurice Mallet, and Chrystel Lopin‐Bon14.1 Introduction 39514.2 O‐ and N‐sulfation in Glycosaminoglycan Glycosaminoglycans Synthesis 39714.3 Protecting Group Strategies for the Synthesis of Sulfated Oligosaccharides of the Proteoglycans Linkage Region 39714.4 Protecting Group Strategy for the Synthesis of Chondroitin Sulfate 40314.5 Protecting Groups in Heparin and HS Synthesis 41514.6 Summary and Conclusions 41914.7 Experimental Part: Procedure for Regioselective 6‐O‐benzoylation Followed by 4‐Sulfation, an Example of the Synthesis of Disaccharide 31 [18] 419Abbreviations 420References 42115 Applications of Fluorous and Ionic Liquid Tags in Oligosaccharide Synthesis 423Imke Sittel and M. Carmen Galan15.1 Introduction 42315.2 Fluorous Supports 42415.3 Ionic Liquid Supports 43615.4 Conclusions 447Abbreviations 447References 44816 Orthogonally Protected Building Blocks for Automated Glycan Assembly 451Fabian Pfrengle and Peter H. Seeberger16.1 Introduction 45116.2 Protecting Groups 45216.3 General Strategy for the Design of Orthogonally Protected Building Blocks 46016.4 “Approved Building Blocks” for Automated Glycan Assembly 46116.5 Solid‐phase Syntheses of Mammalian, Microbial, and Plant Oligosaccharides 46416.6 Chances, Challenges, and Commercialization of Automated Glycan Assembly 467Abbreviations 469References 47017 Kilogram‐scale Production of Synthetic Heparin Analogs: Some Chemical Considerations 473Patrick Trouilleux, Pierre Potier, and Pierre‐Alexandre Driguez17.1 Introduction 47317.2 Kilogram Synthesis of Heparin Building Blocks 47417.3 Experimental Section 48717.4 Summary and Conclusions 489Abbreviations 489References 490Index 493

?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