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Cover
Foreword
Preface
1 Protecting Group Strategies in Carbohydrate Chemistry
1. 1.1 Discriminating Different Functionalities on a Carbohydrate Ring
2. 1.2 Strategies for an (Oligo)saccharide Synthesis Campaign
3. 1.3 Reactivity and Stereochemistry
4. 1.4 Protecting Groups in Automated Synthesis
5. 1.5 Summary and Outlook
6. References
2 Protecting Groups at the Primary Position of Carbohydrates
1. 2.1 Introduction
2. 2.2 Selective Primary Hydroxyl Group Protection
3. 2.3 Selective Primary Hydroxyl Group Deprotection
4. 2.4 Regioselective Transformations at the Primary Position
5. 2.5 Summary and Conclusions
6. 2.6 Experimental Section
7. Abbreviations
8. References
3 Protecting Groups at the Secondary Positions of Carbohydrates
1. 3.1 Introduction
2. 3.2 The Major Protecting Group Motifs
3. 3.3 Conclusion
4. 3.4 Experimental Section
5. Abbreviations
6. References
4 Regioselective Protection at the Secondary Positions of Carbohydrates with Acyclic Protecting Groups
1. 4.1 Introduction
2. 4.2 Regioselective Protections at the 2‐Position
3. 4.3 Regioselective Protections at the 3‐Position
4. 4.4 Regioselective Protections at the 4‐Position
5. 4.5 Regioselective bis‐Protection of the 2,6‐, 3,6‐, and 4,6‐Positions of Hexopyranoside Tetraols
6. 4.6 Regioselective Mono‐deprotection of Peracetyl and Perbenzyl Monosaccharides
7. 4.7 Summary and Conclusions
8. 4.8 Experimental Section
9. References
5 Protecting Groups at the Anomeric Position of Carbohydrates
1. 5.1 Introduction
2. 5.2 O‐alkyl and O‐aryl Glycosides
3. 5.3 Glycosyl Esters
4. 5.4 Cyclic Acetals, Ketals, and Orthoesters
5. 5.5 Silyl Ethers
6. 5.6 S‐glycosyl and N‐glycosyl Derivatives
7. 5.7 Concluding Remarks
8. 5.8 Example Experimental Procedures
9. References
6 N‐protecting Groups for 2‐Amino‐2‐deoxy‐glycosides
1. 6.1 Introduction
2. 6.2 N ‐acyl‐based Protecting Groups
3. 6.3 Imido‐based Protecting Groups
4. 6.4 Carbamate‐based Protecting Groups
5. 6.5 Imine‐ or Enamine‐based Protecting Groups
6. 6.6 2‐Deoxy‐2‐azido Derivatives as a Protecting Group
7. 6.7 From Glycals to 2‐Azido Intermediates
8. 6.8 From Glycals to 2‐Sulfonamido Intermediates
9. 6.9 Summary and Conclusions
10. 6.10 Experimental Section
11. Abbreviations
12. References
7 One‐pot Multistep Regioselective Protection of Carbohydrates Catalyzed by Acids
1. 7.1 Introduction
2. 7.2 Examples of Early Developments of the One‐pot Multistep Regioselective Hydroxyl Protection of Carbohydrates
3. 7.3 One‐pot Multistep Methods from Silylated Substrates
4. 7.4 One‐pot Multistep Methods Catalyzed by Copper Triflate on Unprotected Sugars
5. 7.5 Other One‐pot Multistep Methods Catalyzed by Acids
6. 7.6 Conclusions and Outlook
7. 7.7 Experimental Procedures
8. Acknowledgments
9. References
8 Acyl Migrations in Carbohydrate Chemistry
1. 8.1 Introduction
2. 8.2 Mechanism and Migration Kinetics
3. 8.3 Acyl Group Migration – Synthetic Applications
4. 8.4 Summary and Conclusions
5. 8.5 Selected Experimental Procedures
6. References
9 De Novo Asymmetric Synthesis of Oligosaccharides Using Atom‐less Protecting Groups
1. 9.1 Introduction
2. 9.2 Atom‐less Protecting Groups
3. 9.3 De Novo Approach to Carbohydrates
4. 9.4 O'Doherty Approach to Carbohydrates
5. 9.5 Conclusion
6. 9.6 Experimentals [3]
7. Abbreviations
8. References
10 Protecting Group Strategies for Sialic Acid Derivatives
1. 10.1 Introduction
2. 10.2 Protection of the Carboxylate Group
3. 10.3 Protection of Amine Function
4. 10.4 Selective Protection of Alcohols
5. 10.5 Access to Protected Sialic Acid Derivatives by Total Synthesis
6. 10.6 Access to Protected Sialic Acid Derivatives by Chemoenzymatic Synthesis
7. 10.7 Preparation of Methyl (methyl 5‐acetamido‐3,5‐dideoxy‐D‐glycero‐β‐D‐galacto‐non‐2‐ulopyranosid)onate[20, 22, 104]
8. Abbreviations
9. References
11 Strategies Toward Protection of 1,2‐ and 1,3‐Diols in Carbohydrate Chemistry
1. 11.1 Introduction
2. 11.2 Protection as Cyclic Acetals
3. 11.3 Protection as Orthoesters
4. 11.4 Silylene Acetals as Protecting Groups
5. 11.5 Cyclic Carbonate
6. 11.6 Summary and Conclusions
7. 11.7 Experimental Part: Procedure for Regioselective and Reductive Benzylidene Opening Synthesis of Methyl 2,3,4‐Tri‐O‐benzyl‐α‐D‐glucopyranoside
8. Abbreviations
9. References
12 Protecting Group Strategies Toward Glycofuranoses
1. 12.1 Introduction
2. 12.2 What About Chemistry Without Protecting Groups?
3. 12.3 Protecting Group Interconversion
4. 12.4 Multistep Synthesis of Some Furanosyl‐containing Glycosides and Conjugates
5. 12.5 The Striking Ring Contraction Strategy
6. 12.6 Conclusion Strategy for Synthesizing 4‐Amino‐4‐deoxy and 4‐Deoxy‐4‐thio‐aldose Derivatives
7. References
13 Cyclodextrin Chemistry via Selective Protecting Group Manipulations
1. 13.1 Introduction
2. 13.2 Per‐O‐protection of Cyclodextrins
3. 13.3 Face‐selective Differentiation: Primary vs Secondary Hydroxyl Protection
4. 13.4 Single Hydroxyl Protection Strategies
5. 13.5 Concerted Protection of Hydroxyl Sets (Pairs or Triads)
6. 13.6 Regioselective Deprotection of Symmetric Cyclodextrins
7. 13.7 Summary and Conclusions
8. 13.8 Experimental Procedures
9. Abbreviations
10. References
14 Protecting Group Strategies Toward Sulfated Glycosaminoglycans
1. 14.1 Introduction
2. 14.2 O ‐ and N‐sulfation in Glycosaminoglycan Glycosaminoglycans Synthesis
3. 14.3 Protecting Group Strategies for the Synthesis of Sulfated Oligosaccharides of the Proteoglycans Linkage Region
4. 14.4 Protecting Group Strategy for the Synthesis of Chondroitin Sulfate
5. 14.5 Protecting Groups in Heparin and HS Synthesis
6. 14.6 Summary and Conclusions
7. 14.7 Experimental Part: Procedure for Regioselective 6‐O‐benzoylation Followed by 4‐Sulfation, an Example of the Synthesis of Disaccharide 31[18]
8. References
15 Applications of Fluorous and Ionic Liquid Tags in Oligosaccharide Synthesis
1. 15.1 Introduction
2. 15.2 Fluorous Supports
3. 15.3 Ionic Liquid Supports
4. 15.4 Conclusions
5. References
16 Orthogonally Protected Building Blocks for Automated Glycan Assembly
1. 16.1 Introduction
2. 16.2 Protecting Groups
3. 16.3 General Strategy for the Design of Orthogonally Protected Building Blocks
4. 16.4 “Approved Building Blocks” for Automated Glycan Assembly
5. 16.5 Solid‐phase Syntheses of Mammalian, Microbial, and Plant Oligosaccharides
6. 16.6 Chances, Challenges, and Commercialization of Automated Glycan Assembly
7. References
17 Kilogram‐scale Production of Synthetic Heparin Analogs: Some Chemical Considerations
1. 17.1 Introduction
2. 17.2 Kilogram Synthesis of Heparin Building Blocks
3. 17.3 Experimental Section
4. 17.4 Summary and Conclusions
5. References
Index
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List of Tables

Chapter 02
1. Table 2.1 Regioselective 6‐O‐tritylation.
2. Table 2.2 Selected conditions for the removal of trityl ethers.
3. Table 2.3 Regioselective 6‐O‐silylation.
4. Table 2.4 Removal of TBDMS silyl ethers.
5. Table 2.5 Regioselective 6‐O‐tosylation.
6. Table 2.6 Chemical regioselective 6‐O‐acylation of saccharides.
7. Table 2.7 Chemoenzymatic regioselective 6‐O‐acylation of saccharides.
8. Table 2.8 Regioselective desilylation at the primary position of saccharides.
9. Table 2.9 Chemical regioselective 6‐O‐deacylation of peracylated saccharides.
10. Table 2.10 Chemoenzymatic regioselective 6‐O‐deacylation of peracylated saccharides.
11. Table 2.11 Regioselective 6‐O‐debenzylation of perbenzylated saccharides.
12. Table 2.12 Regioselective halogenation at the primary position of saccharides.
13. Table 2.13 Regioselective oxidation at the primary position of saccharides to carboxylic acids.
14. Table 2.14 Regioselective oxidation at the primary position of saccharides to aldehydes.
Chapter 03
1. Table 3.1 General overview of substituted benzyl groups.
2. Table 3.2 Benzyl protection conditions and functional group compatibility.
3. Table 3.3 Benzyl deprotection conditions and group compatibility.
4. Table 3.4 p‐Methoxybenzyl ether deprotection conditions and group compatibility.
5. Table 3.5 General overview of silyl ethers.
6. Table 3.6 Silyl ether deprotection conditions and group compatibility.
7. Table 3.7 Simple ester protecting groups.
8. Table 3.8 Acetyl deprotection conditions and group compatibility.
9. Table 3.9 Triggered ester protecting groups.
10. Table 3.10 Chloroacetyl deprotection conditions and group compatibility.
Chapter 04
1. Table 4.1 Regioselective 2‐O‐functionalization of glucopyranoside 4,6‐O‐acetals.
2. Table 4.2 Regioselective 2‐O‐functionalization of glucopyranoside 2,3,4‐triols and 2,3,4,6‐tetraols.
3. Table 4.3 Regioselective 2‐O‐functionalization of mannopyranosides.
4. Table 4.4 Regioselective 2‐O‐functionalization of galactopyranosides.
5. Table 4.5 Regioselective 2‐O‐functionalization of other hexopyranosides.
6. Table 4.6 Regioselective 3‐O‐functionalization of glucopyranosides.
7. Table 4.7 Regioselective 3‐O‐functionalization of mannopyranosides.
8. Table 4.8 Regioselective 3‐O‐functionalization of galactopyranosides.
9. Table 4.9 Regioselective 4‐O‐functionalization of hexopyranosides.
10. Table 4.10 Regioselective bis‐functionalization of hexopyranosides.
11. Table 4.11 Regioselective mono‐deprotection of hexopyranosides.
Chapter 05
1. Table 5.1 Installation and removal of alkyl and aryl anomeric protecting groups.
2. Table 5.2 Installation and removal of ester anomeric protecting groups.
3. Table 5.3 Installation and removal of cyclic acetals, ketals, and orthoesters protecting groups.
4. Table 5.4 Installation and removal of silyl ether anomeric protecting groups.
5. Table 5.5 Installation and removal of S‐glycosyl and N‐glycosyl anomeric protecting groups.
Chapter 08
1. Table 8.1 Summary of the O2 → O3 acyl group migration reactions in protected glucopyranosides.
2. Table 8.2 Summary of the O3 → O2 acyl group migration reactions in protected galactopyranosides.
3. Table 8.3 Summary of the investigated acyl group migrations from O4 → O6 (and O3 → O4) in different monosaccharides.
4. Table 8.4 Summary of the displacement–migration reaction sequence of pyranosides and glycals.
5. Table 8.5 A summary of the displacement–migration reaction sequence in furanosides.
6. Table 8.6 Summary of the S6 → O4 acyl migration reaction.
Chapter 12
1. Table 12.1 Reaction conditions for the preparation of 1,2:5,6‐diketalglucofuranose from D‐glucose and 2,3:5,6‐diketalmannofuranose from D‐mannose.
2. Table 12.2 Reaction conditions for the preparation of galactofuranose ketals from D‐galactose.
3. Table 12.3 Reaction conditions for the preparation of other furanose ketals from L‐rhamnose, D‐ or L‐ribose, and D‐xylose.
4. Table 12.4 Reaction conditions for the preparation of diacetone sorbose from L‐sorbose.
5. Table 12.5 Persilylation of D‐galactose by TBDMSCl leads to the sole per‐O‐TBS β‐D‐galactofuranose.
6. Table 12.6 Regioselective acylation of C‐2 position of galactofuranoside and lactone analogs.
7. Table 12.7 Regioselective deacetylation of different pentoses and methyl pentosides.
Chapter 14
1. Table 14.1 Structures of Gal^II–Gal^I sequences reported in this part.
2. Table 14.2 Examples of protection groups used in HS synthesis.
Chapter 16
1. Table 16.1 Selection of PGs recommended for the design of BBs for automated glycan assembly.
Chapter 17
1. Table 17.1 Maltose peracetylation conditions developed at Sanofi compared to the literature.
2. Table 17.2 Benzylidenation conditions of maltoside 19 developed at Sanofi compared to the literature.

List of Illustrations

Chapter 01
1. Scheme 1.1 (A) Relative reactivity of carbohydrate alcohols; (B) four‐step reaction sequence to mask all functional groups in glucosamine; (a) Cl₃CCOCl, Et₃N, and MeOH; (b) (tBu)₂Si(OTf)₂, pyridine, and DMF, −40 °C (86% over 2 steps); (c) CF₃C(=NPh)Cl, Cs₂CO₃, and acetone (98%); (d) LevOH, DIC, DMAP, and DCM (82%). (C) Site‐selective modification of mannosyl hydroxyl groups; (e) Ac₂O and pyridine; (f) PhSH, BF₃·OEt₂, and DCM (75% over 2 steps); (g) NaOMe and MeOH (100%); (h) HBF₄·OEt₂, PhCH(OMe)₂, and DMF (60%); (i) Bu₄NHSO₄, BnBr, NaOH, and DCM (75%); (j) (i) Bu₂SnO, toluene, and reflux; (ii) CsF, Bu₄NBr, PMBCl, toluene, and reflux (94%).
2. Scheme 1.2 Borinic acid catalysis to regioselectively protect alcohol functionalities: (a) 8; (b) BnBr, Ag₂O, and MeCN, 40 °C, 48 h (94%); (c) BzCl, iPr₂NEt, and MeCN (92%).
3. Scheme 1.3 One‐pot protection of per‐silylated thioglycoside to form different protected building blocks 13–15.
4. Scheme 1.4 Block coupling to heparin‐like 20‐mers. (a) Pd(OH)₂/C and EtOH/H₂O (89%); (b) SO₃·Pyridine and H₂O.
5. Scheme 1.5 GPI synthesis using a global deprotection strategy based on PMB protecting groups. (a) Zn, AcOH, and CH₂Cl₂, 2 h; (b) DBU and CH₂Cl₂, 1 h; (c) CH₂Cl₂‐TFA (9 : 1), 1 h, 81% (3 steps).
6. Scheme 1.6 Global deprotection using TFA in toluene: (a) TMSOTf and DCM, −20 °C (97%); (b) HF/pyridine and pyridine (91%); (c) 28, TMSOTf, and DCM, −20 °C (94%); (d) TFA/toluene (10 : 1, v/v), 0 °C to RT (100%).
7. Scheme 1.7 (A) The armed–disarmed concept using n‐pentenyl glycosides as conceptualized by Fraser‐Reid. (B) Exploiting donor reactivity in a one‐pot reaction sequence. (a) TfOH and NIS, −25 °C, DCM; (b) NIS, 0 °C, DCM; (c) NIS and DCM (40%).
8. Scheme 1.8 Neighboring group participation‐assisted selective activation: (a) Cu(OTf)₂, TfOH, and DCM (70%).
9. Scheme 1.9 Reaction mechanism manifold to account for the stereoselectivity in glycosylation reactions of benzylidene mannose donors.
10. Scheme 1.10 (A) Hydrogen‐bonding acceptor delivery by picolinyl and picolinoyl ether; (B) hydrogen‐bonding acceptor delivery by cyanobenzyl ethers.
11. Scheme 1.11 Automated synthesis of oligomannuronic acids. (A) Solid‐phase approach. (B) Fluorous‐phase approach.
12. Scheme 1.12 Automated solid‐phase assembly of hyaluronic acid oligosaccharides.
13. Scheme 1.13 Automated solid‐phase assembly of plant cell wall arabinoxylan fragments; (a) donor 86, TMSOTf, and DCM, −35 °C to −15 °C; (b) donor 87, TMSOTf, and DCM, −35 °C to −15 °C; (c) donor 88, NIS/TfOH, and DCM/dioxane, −40 °C to −20 °C; (d) donor 89, NIS/TfOH, and DCM/dioxane, −40 °C to −20 °C; (e) 20% Et₃N in DMF, 25 °C; (f) 0.1 M DDQ in DCE/MeOH/H₂O (64 : 16 : 1); (g) Ac₂O and pyridine, 25 °C; (h) hv (305 nm); (i) NaOMe and THF/MeOH; (j) H₂, Pd/C, and EtOAc/MeOH/H₂O/AcOH.
14. Scheme 1.14 Selective deprotection of AzDMB and MPDMB pivaloyl analogues.
15. Scheme 1.15 Birch reduction of teichuronic acid oligosaccharides in which cleavage of the mannosaminuronic acid linkages was encountered; (a) Na (s), liquid NH₃, and THF, −60 °C; (b) HPLC purification; (c) Ac₂O, NaHCO₃, and THF/H₂O (97: 35% over 2 steps; 98: 14% over 2 steps).
Chapter 02
1. Figure 2.1 General outlook of the regioselective and/or chemoselective protections and chemical transformations possible at the primary position of saccharides.
Chapter 03
1. Scheme 3.1 Different protecting group roles in a hypothetical oligosaccharide synthesis.
Chapter 06
1. Figure 6.1 Structure of the three main blood group antigens O, A, and B conjugated to their protein.
2. Figure 6.2 General structures of glycosaminoglycans and their sulfated species.
3. Figure 6.3 General aspects of glycosylation with 2‐acetamido‐2‐deoxy‐glycosides.
4. Scheme 6.1 Introduction of the trichloroacetyl protecting group.
5. Scheme 6.2 Reduction of the trichloroacetyl protecting group to the acetyl moiety.
6. Scheme 6.3 Introduction of the trifluoroacetyl protecting group.
7. Scheme 6.4 Hydrolysis of the trifluoroacetyl protecting group.
8. Scheme 6.5 Installation of the phthaloyl protecting group.
9. Scheme 6.6 Aminolysis of the phthaloyl protecting group.
10. Scheme 6.7 Installation of the dichlorophthaloyl protecting group.
11. Scheme 6.8 Installation of the tetrachlorophthaloyl protecting group.
12. Scheme 6.9 Installation of the dithiasuccinyl protecting group.
13. Scheme 6.10 Installation of the thiodiglycolyl protecting group.
14. Scheme 6.11 Installation of the diphenylmaleoyl protecting group.
15. Scheme 6.12 Installation of the dimethylmaleoyl protecting group.
16. Scheme 6.13 Installation of the 2,2,2‐trichloroethoxycarbonyl protecting group.
17. Scheme 6.14 Removal of the 2,2,2‐trichloroethoxycarbonyl protecting group.
18. Scheme 6.15 Installation of the benzyloxycarbonyl protecting group.
19. Scheme 6.16 Installation of the allyloxycarbonyl protecting group.
20. Scheme 6.17 Removal of the 2,2,2‐trichloroethoxycarbonyl protecting group.
21. Scheme 6.18 Installation of the t‐butoxycarbonyl protecting group from 2‐amino‐ or 2‐azido‐2‐deoxy‐glycosides.
22. Scheme 6.19 Installation of the t‐butoxycarbonyl protecting group from 2‐acetamido‐2‐deoxy‐glycosides.
23. Scheme 6.20 Installation of the 9‐fluorenylmethoxycarbonyl protecting group.
24. Scheme 6.21 Installation of the 2,3‐oxazolidinone protecting group.
25. Scheme 6.22 Removal of the 2,3‐oxazolidinone protecting group from N‐H or N‐Ac precursors.
26. Scheme 6.23 Removal of the 2,3‐oxazolidinone protecting group from N‐Bn precursors.
27. Scheme 6.24 Synthesis of N‐arylidene glycosides.
28. Scheme 6.25 Synthesis of Ddm‐ and Dde‐protected glycosides.
29. Scheme 6.26 Synthesis of DTPM‐protected glycosides.
30. Scheme 6.27 Conversion of 2‐amino‐glycosides into 2‐azido‐glycosides.
31. Scheme 6.28 Conversion of 2‐azido‐glycosides into 2‐amino‐glycosides.
32. Scheme 6.29 Conversion of glycals into 2‐azido‐glycosides.
33. Scheme 6.30 Conversion of glycals into 2‐sulfonamido‐glycosides.
Chapter 07
1. Scheme 7.1 One‐pot preparation of fully protected glycopyranosides according to Helferich (1923–1927), Micheel or Wolfrom (1934), and Kong (2000).
2. Scheme 7.2 One‐pot preparation of per‐O‐acetylated thioglycosides from the unprotected reducing sugars.
3. Scheme 7.3 Per‐O‐trimethylsilylation of the glycopyranosides for the one‐pot regioselective protection.
4. Scheme 7.4 Copper(II) triflate‐catalyzed one‐pot multistep regioselective protection of per‐O‐trimethylsilylated‐D‐glucopyranosides 15, 16.
5. Scheme 7.5 Probable mechanism for the one‐pot multistep preparation of the 3,4‐di‐O‐benzyl‐protected monosaccharide 21.
6. Scheme 7.6 Trimethylsilyltriflate‐catalyzed one‐pot regioselective preparation of the fully protected monosaccharides 25 and 26.
7. Scheme 7.7 Examples of trimethylsilyltriflate‐catalyzed one‐pot regioselective protection starting from per‐O‐trimethylsilylated 4‐methylphenyl 1‐thio‐β‐D‐glucopyranoside 24.
8. Scheme 7.8 Trimethylsilyltriflate‐catalyzed benzylidenation of per‐O‐trimethylsilylated 4‐methylphenyl 1‐thio‐α‐D‐mannopyranoside 31.
9. Scheme 7.9 Examples of trimethylsilyltriflate‐catalyzed one‐pot regioselective protection starting from per‐O‐trimethylsilylated 4‐methylphenyl 1‐thio‐α‐D‐mannopyranoside 31.
10. Scheme 7.10 One‐pot regioselective protection starting from the per‐O‐silylated 2‐azido‐2‐deoxy‐D‐glucopyranose 38.
11. Scheme 7.11 One‐pot regioselective protection starting from the per‐O‐silylated 2‐azido (or 2‐acetamido)‐2‐deoxy‐β‐D‐glucopyranosides 41 and 42.
12. Scheme 7.12 Trimethylsilyltriflate‐catalyzed one‐pot regioselective protection starting from the per‐O‐silylated thio‐β‐D‐xylo‐ and D‐galacto‐ derivatives.
13. Scheme 7.13 Two examples of one‐pot three‐step transformations catalyzed by iron(III) chloride hexahydrate.
14. Scheme 7.14 Tandem iron(III) chloride hexahydrate‐catalyzed regioselective protection of silylated α,α‐D‐trehalose 53 and methyl α‐maltoside 57.
15. Scheme 7.15 Tandem iron(III) chloride hexahydrate‐catalyzed regioselective protection of per‐O‐silylated methyl β‐maltotrioside 59.
16. Scheme 7.16 Triflic acid on molecular sieves‐catalyzed one‐pot regioselective protection of tri‐O‐trimethylsilylated glucosamine derivatives 61.
17. Scheme 7.17 Copper triflate‐catalyzed one‐pot multistep protection of unprotected D‐glycopyranosides 64.
18. Scheme 7.18 Iodine‐catalyzed tandem acetalation–acetylation of unprotected D‐mannose.
19. Scheme 7.19 HClO₄–silica or H₂SO₄–silica‐catalyzed one‐pot acetalation–esterification of O‐ and S‐glycosides.
20. Scheme 7.20 p‐Toluenesulfonic acid or iodine‐catalyzed one‐pot acetalation/esterification of O‐ and S‐glycopyranosides.
Chapter 08
1. Scheme 8.1 Tentative mechanism of acyl group migration under basic conditions.
2. Figure 8.1 Acylated galactose model compounds utilized for acyl migration studies.
3. Figure 8.2 Migration of acetyl group (compound 1) at pD = 8.0 and T = 25 °C in buffered D₂O.
4. Scheme 8.2 Migration of acetyl groups in β‐D‐galactopyranoside model compounds.
5. Scheme 8.3 Migration of pivaloyl groups in mannopyranosides and glucopyranosides. Reaction conditions: (i) Ag₂O, TBAI, DMF, 60 °C, 12 h, 58% or CF₃CO₂Cs, TBAI, DMF, 55 °C, 10 h, 67% or Ag₂O, TBAI, DMF, RT, sonication, 4 min, 81% and (ii) Ag₂O, TBAI, DMF, RT, 48 h, 49%.
6. Scheme 8.4 Acyl group migration in chiro‐inositol utilizing phenylboronic acid as a selector. Reaction conditions: (i) DBU, MeCN, mixture of compounds or DBU, PhB(OH)₂, MeCN, 72% of indicated structure.
7. Scheme 8.5 Acyl group migration in myo‐inositol utilizing phenylboronic acid or boric acid as a selector. Reaction conditions: (i) DBU, boric acid, MeCN, 83% of the thermodynamic product and (ii) DBU, PhB(OH)₂, MeCN, 92% of the kinetic product.
8. Scheme 8.6 Reaction conditions: (i) (1) Tf₂O, pyridine; (2) H₂O, Δ, 75%.
Chapter 09
1. Scheme 9.1 The role of protecting groups in traditional oligosaccharide synthesis.
2. Scheme 9.2 The various de novo approaches to hexoses.
3. Scheme 9.3 Asymmetric synthesis of furan alcohols and pyranones.
4. Scheme 9.4 De novo asymmetric approach to α‐L‐manno‐, talo‐, and gulo‐pyranose.
5. Scheme 9.5 De novo asymmetric approach to deoxy‐pyranones.
6. Scheme 9.6 Application of the Wharton rearrangement for the synthesis of rare sugars.
7. Scheme 9.7 Use of pyran‐2‐ones for the de novo synthesis of pyranoses.
8. Scheme 9.8 De novo access to 2‐epi‐, idose‐, rhamno‐colitose.
9. Scheme 9.9 Palladium‐catalyzed glycosylation.
10. Scheme 9.10 De novo synthesis and use of pyranone‐based glycosyl donor.
11. Scheme 9.11 De novo synthesis of 1,6‐linked mannose disaccharide and trisaccharides.
12. Scheme 9.12 De novo synthesis of 1,4‐linked mannose disaccharide and trisaccharides.
13. Scheme 9.13 De novo synthesis of a library of D‐/L‐1,4‐linked α‐rhamno‐trisaccharides.
14. Scheme 9.14 Synthesis of highly branched 1,4‐/1,6‐heptasacharides.
15. Scheme 9.15 Synthesis of glycosylated tyrosine portion of mannopeptimycin‐ε.
16. Scheme 9.16 Synthesis of the trisaccharide portion of PI‐080.
17. Scheme 9.17 Cleistriosides and cleistetrosides family of natural products.
18. Scheme 9.18 Retrosynthetic route to cleistetrosides and cleistriosides.
19. Scheme 9.19 Preparation of trisaccharide intermediate 107 for the syntheses of cleistriosides and cleistetrosides.
20. Scheme 9.20 Example of divergent synthesis of cleistrioside and cleistetrosides.
21. Scheme 9.21 Mezzettiaside family of natural products.
22. Scheme 9.22 Retrosynthetic scheme for the divergent synthetic route to mezzettiasides.
23. Scheme 9.23 Synthesis of key intermediate toward divergent synthesis of mezzettiasides.
24. Scheme 9.24 Divergent synthesis of mezzettiaside disaccharides.
25. Scheme 9.25 Divergent route to mezzettiaside trisaccharides.
26. Scheme 9.26 Synthesis of mezzettiaside tetrasaccharide.
Chapter 10
1. Scheme 10.1 Formation of the peracetyl methyl ester.
2. Scheme 10.2 Selective cleavage of methyl ester.
3. Scheme 10.3 Formation and cleavage of allyl esters.
4. Scheme 10.4 Formation and cleavage of phenacyl esters.
5. Scheme 10.5 Preparation of thioesters.
6. Scheme 10.6 Amide formation and cleavage.
7. Scheme 10.7 Intra‐residue lactone formation.
8. Scheme 10.8 Inter‐residue lactone formation.
9. Scheme 10.9 Lactam formation and cleavage.
10. Scheme 10.10 Formation of spirocyclic hydantoins.
11. Scheme 10.11 Acidic cleavage of the acetamide and reinstallation of an amide group.
12. Scheme 10.12 Amide cleavage under basic conditions.
13. Scheme 10.13 Cleavage of the acetamide by prior installation of a Boc group.
14. Scheme 10.14 Installation of the acetamide function.
15. Scheme 10.15 Installation of the isothiocyanate moiety.
16. Scheme 10.16 Isothiocyanate manipulation.
17. Scheme 10.17 Installation of O4,N5‐oxazolidinone and N‐acetyloxazolidinone.
18. Scheme 10.18 Cleavage of the O4,N5‐oxazolidinone and N‐acetyloxazolidinone.
19. Scheme 10.19 Installation of the O7,N5‐oxazinone.
20. Scheme 10.20 Selective acylation of the primary alcohol.
21. Scheme 10.21 Selective methylation of the primary alcohol.
22. Scheme 10.22 Selective silylation reactions.
23. Scheme 10.23 Selective acetonide formation and subsequent selective acetylation, silylation, and alkylation.
24. Scheme 10.24 Selective formation of 7‐O‐, 7,9‐di‐O‐, and 7,8,9‐tri‐O‐acetyl derivatives.
25. Scheme 10.25 Installation of arylidene acetals under kinetic conditions with subsequent reductive ring opening.
26. Scheme 10.26 Installation and manipulation of a 7,9‐O‐benzylidene acetal.
27. Scheme 10.27 Silylene and disiloxane installation.
28. Scheme 10.28 Selective O → N‐acetyl migration.
29. Scheme 10.29 Selective replacement of trimethylsilyl ethers by acetyl groups.
30. Scheme 10.30 Biosynthesis of N‐acetylneuraminic acid.
Chapter 11
1. Scheme 11.1 Methylene acetal formation from methyl tri‐O‐benzyl‐β‐D‐glucopyranoside (i) (HCHO)_n, pTsOH, toluene, 110 °C, 67%; (ii) CH₂Br₂ 2 eq., KOH 8 eq., DMSO, RT, 39%; (iii) PhSCH₂OMe, DBDMH, BHT, MeCN, RT, 85%.
2. Scheme 11.2 Hydrolysis of methylenedioxy acetals (i) AcOH, TFAA, 26 °C, 3 h and (ii) NaOH 1 N, MeOH/H₂O 9/1, 1 h (90% from 4, 89% from 5).
3. Scheme 11.3 Formation, deprotection, and reduction of a PSE‐glucopyranose derivative (i) NaH, 1,2‐bis(phenylsulfonyl)ethylene, Bu₄NBr; (ii) DIBAL‐H, toluene then acetylation; and (iii) LiAlH₄ or LiAlH₄, AlCl₃.
4. Scheme 11.4 Synthesis of diacyltrehalose 12 (i) DMC, pTsOH, 60 °C, 140 mbar, 69%; (ii) palmitic acid, DCC, DMAP, CH₂Cl₂, 92%; and (iii) AcOH, MeOH; 60 °C, 50%.
5. Scheme 11.5 Regioselective protection of 1,2‐cis‐diol: synthesis of 3,4‐O‐isopropylidene‐β‐D‐galactopyranoside 14.
6. Scheme 11.6 D‐Mannose‐based scaffolds (i) TFA, 76% and (ii) TFA/MeOH 1/1, 90% [29].
7. Scheme 11.7 Protection of 1,2‐trans diols with diacetals
8. Scheme 11.8 Selective benzylidene deprotection and in situ oxidation of the primary position of the D‐glucopyranoside 23 to a glucuronic derivative 24: (i) RuCl₃ (20 mol%), NaIO₄ (10 eq.) CH₃CN/CCl₄/H₂O, 3.5 h, 61%.
9. Scheme 11.9 Thiourea and squaramide as organocatalysts in benzylidene acetal formation.
10. Scheme 11.10 Introduction of a MOM protecting group via an orthoester intermediate 24: (i) (MeO)₃CH, CH₂Cl₂, CAN then (ii) DIBAL‐H, −78 °C, 92% of 25a/25b as a 1/1 mixture.
11. Scheme 11.11 Synthesis of 5‐exo‐methylene mannofuranose derivative (i) (MeO)₃CH, p‐TsOH·H₂O_cat. then (ii) Ac₂O, reflux, 88%.
12. Scheme 11.12 Kinetically controlled orthoesterification: (i) 1,1‐dimethoxyethene, p‐TsOH_cat., DMF, 0 °C.
13. Scheme 11.13 Hydrolysis of bis‐orthoester 37: (i) PhC(OEt)₃, p‐TsOH, TFA, MeCN, RT, 2 h; (ii) TFA/H₂O, MeCN, RT, 10 min [70a].
14. Scheme 11.14 Tricyclic dichloroacetyl orthoesters: (i) tBuOK (3 eq.), tBuOH, reflux, 40 min; (ii) tBuOK (1.5 eq.), reflux, 6 h.
15. Scheme 11.15 Synthesis of D‐digitalose 44: IR‐120 H⁺, H₂O/MeOH.
16. Scheme 11.16 Application of a di‐t‐butylsilene in glycosylation methodology: (i) NIS, TfOH, MS 4 Å, −78 to −50 °C, 2–3 h, CH₂Cl₂.
17. Scheme 11.17 Diisopropylsilanyl group application in nucleoside chemistry [81]: formation (i) TIPDSCl₂, imidazole, DMF; removal (ii) TBAF, THF.
18. Scheme 11.18 Incorporation of the bis‐silyl (SIBA) protecting group: (i) imidazole, DMF, 0 °C to RT.
19. Scheme 11.19 1,2‐Diol protection with a TIPDS group: (i) TIPDSCl₂, imidazole, DMF, −40 °C.
20. Scheme 11.20 Cyclic carbonate formation via intramolecular substitution of transient triflate derivative: (i) Tf₂O, pyridine, CH₂Cl₂, −40 to 0 °C; (ii) DMF, pyridine, 65 °C; and (iii) AcOH, dioxane, H₂O.
21. Scheme 11.21 Catalytic formation of a bis‐cyclic carbonate on D‐glucose: (i) PdI₂, KI, MeC(OMe)₃, DMA.
Chapter 12
1. Scheme 12.1 Fischer glycosylation.
2. Figure 12.1 Examples of glycosylation of simple alcohols.
3. Scheme 12.2 Acetolysis of furanosides.
4. Scheme 12.3 Synthesis of 1‐thiofuranosides.
5. Scheme 12.4 Preparation of alkyl α‐D‐galactofuranosides.
6. Figure 12.2 Structure of some lactones.
7. Scheme 12.5 Representative ketalization of sugars toward furanoside or pyranoside forms.
8. Scheme 12.6 Ketalization of D‐glucose toward 1,2:5,6‐diketalglucofuranose.
9. Scheme 12.7 Ketalization of D‐mannose toward 2,3:5,6‐diketalmannofuranose.
10. Scheme 12.8 Ketalization of D‐galactose toward 1,2:5,6‐diketalgalactofuranose and 1,2:3,4‐diketalgalactopyranose.
11. Scheme 12.9 Ketalization of D‐rhamnose, D‐ribose, and D‐xylose.
12. Scheme 12.10 Ketalization of L‐sorbose toward 1,2 : 3,5‐disopropylidenesorbofuranose.
13. Scheme 12.11 Products of acetylation of pentoses and hexoses.
14. Scheme 12.12 Obtention of per‐O‐acyl galactofuranoses.
15. Scheme 12.13 Conditions of acylation of fructose that favor the furanose forms.
16. Scheme 12.14 Acetylation of glucose in the presence of boric acid leads to per‐O‐acetyl glucofuranose.
17. Scheme 12.15 Selective silylation of D‐arabinofuranose.
18. Scheme 12.16 Examples of selective acylation of primary alcohol of furanoside.
19. Scheme 12.17 Regioselective acylation at positions 2 and 5 according to the base.
20. Scheme 12.18 Regioselective acylation of position 5 of pentoses.
21. Scheme 12.19 Regioselective acetylation and deacetylation of D‐fructose.
22. Scheme 12.20 The TIPS protecting group for nucleoside synthesis.
23. Scheme 12.21 Influence of the DTBS group on the anomeric position.
24. Scheme 12.22 Influence of the silyl protecting group on the reactivity of the anomeric position.
25. Scheme 12.23 The galactono‐1,4‐lactone as a key intermediate in the synthesis of galactofuranosyl‐containing saccharides and conjugates.
26. Scheme 12.24 Synthesis of analogs of UDP‐Galf.
27. Scheme 12.25 Synthesis of α‐D‐fucofuranosides.
28. Scheme 12.26 Synthesis of agelagalastatin.
29. Scheme 12.27 2,3‐Epoxides as protecting group.
30. Scheme 12.28 Isomerization of UPD‐Galp into UDP‐Galf assisted by a mutase in the presence of NADPH.
31. Scheme 12.29 Selective opening of 1,4‐anhydrogalactopyranose.
32. Scheme 12.30 Pyranose–furanose rearrangement from KDN donor.
33. Scheme 12.31 The pyranose‐to‐furanose rearrangement.
Chapter 13
1. Figure 13.1 (a) General structure and pictographic representation of native CDs, with an indication of averaged dimensions (i.d. and o.d. are the inner and outer diameter, respectively), (b) axial, and (c) side views of βCD highlighting hydroxyl location orientation and main features.
2. Scheme 13.1 Strategies toward regioselective protection of all hydroxyls at primary rim with bulky (a) silylating [17, 18], (b) acylating [12, 19], and (c) alkylating agents [20].
3. Scheme 13.2 Strategies toward protection of secondary rim hydroxyls implementing (a) TMSOTf‐catalyzed acetolysis of benzyl ethers at the primary rim [26]. (b) Regioselective transesterification of benzoates from the primary to the secondary rim [27]. (c) Indirect orthogonal protection/deprotection of primary rim hydroxyls [17].
4. Scheme 13.3 Strategies toward differentiation of secondary OH‐2 vs OH‐3 hydroxyls by (a) regioselective alkylation [13b, 34] and dealkylation [35], (b) silylether group manipulation [16, 18, 21, 36, 37], and (c) asymmetric ketal formation [38].
5. Scheme 13.4 Strategies toward selective hydroxyl monoprotection (a) at OH‐6 [43, 44], (b) OH‐2 [36, 45], and (c) OH‐3 hydroxyls [46, 47].
6. Scheme 13.5 Strategies for the concerted protection of hydroxyl sets using (a) tritylating [25a, 51, 52b, 53] and (b) bis‐tritylating [54, 55] reagents.
7. Scheme 13.6 Strategies for the concerted protection of hydroxyl sets using (a) benzylating reagents. (b) Benzylidene ketals.
8. Scheme 13.7 (a) Structural requirements for DIBALH‐promoted debenzylation with the indication of the hypothesized intermediates. (b) Implementation of DIBALH‐promoted regioselective debenzylation reaction toward concerted cleavage of distal O‐6 benzyl groups in CDs. (c) Tri‐, tetra‐, and orthogonally hexadifferentiated αCDs.
9. Scheme 13.8 DIBALH‐promoted regioselective desilylation of primary hydroxyls.
10. Scheme 13.9 DIBALH‐promoted regioselective demethylation of secondary hydroxyls [78, 79].
Chapter 14
1. Figure 14.1 Schematic representation of principal steps of PG‐GAG chain synthesis.
2. Figure 14.2 Structure of the Gal^II–Gal^I sequence.
3. Scheme 14.1 Synthesis of 4‐ and 6‐sulfated products via a 4,6‐diol.
4. Figure 14.3 Structure of disaccharide 1 and trisaccharide 10 synthesized by Jacquinet's group.
5. Scheme 14.2 Synthesis of various sulfoforms following the first strategy. (i) 90% TFA, RT, 15 min; (ii) PhCOCl, pyridine, RT, 16 h; and (iii) hydrazinium acetate, pyridine, RT, 8 min.
6. Figure 14.4 Structure of the GlcA‐Gal^II–Gal^I compounds synthesized by Jacquinet's group.
7. Scheme 14.3 Synthesis of 4‐ and 6‐sulfated products based on temporary protection.
8. Figure 14.5 Structure of the CS disaccharide units.
9. Scheme 14.4 Synthesis of CS‐A, ‐C, and ‐E starting from a 4,6‐diol.
10. Scheme 14.5 Synthesis of CS‐A and ‐C disaccharides. (i) AcOH‐H₂O, 100 °C, 87%; (ii) BzCN, pyridine, 93%; (iii) SO₃·NMe₃, DMF, 50 °C, then [Na⁺] ion exchange, 90%; and (iv) LiOH/H₂O₂, THF/H₂O, then NaOH, 80–82%.
11. Scheme 14.6 Synthesis of CS‐E oligosaccharides. (i) CSA, CH₂Cl₂‐MeOH, 80%; (ii) SO₃·NMe₃, DMF, 50 °C, then [Na⁺] ion exchange, 91–95%; and (iii) LiOH, THF/H₂O, then NaOH, 70–75%.
12. Scheme 14.7 Synthesis of CS‐A, ‐C, or ‐E using different protecting groups on the GalN unit. (i) DDQ, H₂O‐CH₃CN, 93%. (ii) Thiourea, pyridine‐EtOH, then Bu₃SnH, AIBN, benzene, 71–91%.
13. Scheme 14.8 Synthesis of CS‐E tetrasaccharide. (i) (HF)_n·Pyr, THF, 0 °C, 100%; (ii) SO₃·NMe₃, DMF, 100 °C, microwave (MW) irradiation, then [Na⁺] ion exchange, 95%; (iii) LiOH, THF/H₂O, then NaOH, then Ac₂O, MeOH, Et₃N, 62%; and (iv) H₂, Pd(OH)₂/C, H₂O/MeOH, 92%.
14. Scheme 14.9 Reductive opening of benzylidene acetal. (i) HCl, NaBH₃CN, THF, 51%.
15. Scheme 14.10 Synthesis of CS‐A and ‐C using orthoester strategy. (i) BzCl, CH₂Cl₂‐pyridine, 91%; (ii) TFA‐H₂O, CH₂Cl₂, 84%; (iii) PhC(OMe)₃, CSA then 80% AcOH, 35% for 6‐Bz, 37% for 4‐Bz; and (iv) (ClAc)₂O, CH₂Cl₂‐pyridine, 90% for 53, 87% for 54.
16. Scheme 14.11 Synthesis of CS‐D oligosaccharides.
17. Scheme 14.12 Synthesis of CS‐D, ‐K, ‐M, ‐L disaccharides. (i) BzCN, pyridine, 80%; (ii) Bu₂SnO, dioxane–benzene, then BzCl, 68%; (iii) Bu₃SnH, AIBN, benzene–DMAC, then 80% AcOH, 80%; (iv) BzCN, pyridine, then SO₃·NMe₃, DMF, 60 °C then [Na⁺] ion exchange, 80%; (v) SO₃·NMe₃, DMF, 40 °C, then [Na⁺] ion exchange, 75%; and (vi) SO₃·NMe₃, DMF, 60 °C, then [Na⁺] ion exchange, 90%.
18. Scheme 14.13 Synthesis of all types of CS disaccharides. (i) TFA/H₂O, CH₂Cl₂, 95%; (ii) Et₃SiH, TfOH, CH₂Cl₂, 88%; (iii) Et₃SiH, PhBCl₂, CH₂Cl₂, 97%; (iv) DDQ, H₂O, CH₂Cl₂; and (v) NaOH, MeOH/THF.
19. Scheme 14.14 Regular heparin synthesis.
20. Scheme 14.15 Reagents and conditions: (i) 3% TMSOTf, CH₂Cl₂, 79%; (ii) EtSH, PTSA (cat.), 75%; (iii) BzCN, Et₃N (cat.), MeCN, −40 °C, 93%; (iv) 3% TMSOTf, 58%; (v) KOH, 74%; and (vi) SO₃·NMe₃; Dowex 50WX4 (Na⁺), 71%, then H₂ 10% Pd/C then SO₃·Pyr, 87%.
21. Scheme 14.16 Reagents and conditions (i) N₂H₄·HOAc, toluene/EtOH, 90%; (ii) SO₃·Pyr, DMF; (iii) (a) LiOH, H₂O₂, THF, then 4 M NaOH, MeOH, 58%; (iv) PMe₃, THF, NaOH, 65%; and (v) SO₃·Pyr, MeOH, Et₃N, 0.1 M NaOH, 50%, then H₂, Pd/C, MeOH/H₂O.
Chapter 15
1. Scheme 15.1 Two different simple purification strategies: (a) liquid–liquid extraction; (b) fluorinated solid‐phase extraction (FSPE).
2. Scheme 15.2 Most common reactions to install an FTag to a monosaccharide unit.
3. Scheme 15.3 First use of a fluorinated protecting group in oligosaccharide synthesis for purification purposes.
4. Scheme 15.4 FTag‐assisted monosaccharide building block synthesis.
5. Scheme 15.5 Different cleavage strategies with a pentenyl‐based FTag.
6. Scheme 15.6 One‐pot synthesis of Lewis^X (a) and general catch‐and‐release mechanism (b).
7. Scheme 15.7 Step‐wise assembly of branched hexasaccharide with full stereocontrol on a fluorous support.
8. Scheme 15.8 Ester‐based, heavy FTag‐assisted synthesis of disaccharides.
9. Scheme 15.9 Di‐FTagged strategy: donor and acceptor bound.
10. Scheme 15.10 Di‐FTagged strategy: donor bound.
11. Scheme 15.11 Combinatorial oligosaccharide synthesis using different FTags to aid purification and separation.
12. Scheme 15.12 Froc as fluorinated amino protecting group in oligosaccharide synthesis.
13. Scheme 15.13 Fluorinated silyl protecting group in oligosaccharide synthesis.
14. Scheme 15.14 Fluorinated phosphate protecting group in the synthesis of sugar phosphates.
15. Scheme 15.15 Formation of ionic liquid tag (ITag).
16. Scheme 15.16 ITag‐supported oligosaccharide synthesis and product purification.
17. Scheme 15.17 Ester‐linked ITags at C‐4 or C‐6 (a) and ether‐linked ITags to the anomeric position (b).
18. Scheme 15.18 Attachment (a) and cleavage (b) of ester‐linked ITags.
19. Scheme 15.19 Initial reports of ITagged oligosaccharide synthesis by the groups of Chan (a) and Wang (b).
20. Scheme 15.20 ITag‐assisted synthesis of a linear α‐1,6‐linked tetramannoside.
21. Scheme 15.21 ITag‐assisted synthesis of linear α‐1,4‐linked oligosaccharides.
22. Scheme 15.22 General procedure for ITag attachment at the anomeric position via an ether linkage.
23. Scheme 15.23 Ionic catch‐and‐release oligosaccharide synthesis (ICROS).
24. Scheme 15.24 Cleaving conditions for propyl ether‐linked ITag3 (a), synthesis of a linear tetrasaccharide using the ICROS methodology (b), and benzyl ether‐linked ITag4 (c).
25. Scheme 15.25 Combinatorial ICROS.
26. Scheme 15.26 Synthesis of linear α‐1,2‐linked nonamannoside.
27. Scheme 15.27 Synthesis of protected chitotetrasaccharide.
28. Scheme 15.28 Disulfide‐based (a) and arylsulfonamide‐based (b) MS probes.
29. Scheme 15.29 ITags in enzymatic oligosaccharide synthesis [39, 40].
Chapter 16
1. Scheme 16.1 Overview of the automated glycan assembly process.
2. Figure 16.1 Base‐labile, metathesis‐labile and photo‐labile linkers for SPOS.
3. Figure 16.2 Participating PGs for the formation of 1,2‐trans β‐glycosidic bonds.
4. Scheme 16.2 α‐Selective BBs in the automated glycan assembly of the tumor associated antigen Globo‐H and a xyloglucan‐related trisaccharide.
5. Scheme 16.3 A chiral auxiliary in the C2‐position enhances the α‐selectivity in glucosidation reactions on solid phase.
6. Scheme 16.4 A benzylidene protected mannose BB promotes the preferential formation of β‐mannosides.
7. Scheme 16.5 Automated glycan assembly of β‐mannuronic acid alginates.
8. Scheme 16.6 Azide protected BB 7 in the SPOS of heparin sulfate precursors.
9. Figure 16.3 Cyclic PGs for the permanent protection of glucosamine BBs.
10. Figure 16.4 Selection of BBs bearing Fmoc as temporary PG.
11. Figure 16.5 BBs equipped with Lev, Alloc and acetyl as participating temporary PGs.
12. Figure 16.6 BBs equipped with Nap, TBS, and Tom as nonparticipating temporary PGs.
13. Scheme 16.7 Nitrophtalimidobutyric acid (NPB) for monitoring glycosylation efficiency by colorimetric determination of nitrophthalhydrazide production during deprotection.
14. Scheme 16.8 Capping strategy to reduce the number of required temporary orthogonal PGs in automated glycan assembly.
15. Figure 16.7 Selection of building blocks that have been successfully used in automated glycan assembly.
16. Scheme 16.9 Synthesis of orthogonally protected galactose BB 11.
17. Scheme 16.10 Synthesis of orthogonally protected xylose BB 14.
18. Scheme 16.11 Automated glycan assembly of a Lewis‐X pentasaccharide.
19. Scheme 16.12 Automated glycan assembly of a branched oligoarabinofuranoside from the mycobacterial cell envelope.
20. Scheme 16.13 Automated glycan assembly of a plant arabinogalactan oligosaccharide.
Chapter 17
1. Figure 17.1 Schematic representation of the antithrombin‐binding domain (grey) in a HPN/HS polysaccharide.
2. Figure 17.2 Schematic representation of the antithrombin‐binding domain (dark grey) in idrabiotaparinux (1) and hexadecasaccharide 2.
3. Scheme 17.1 Retrosynthesis of the antithrombin‐binding domain (dark grey) of idrabiotaparinux (1) and hexadecasaccharide 2 (final steps).
4. Scheme 17.2 Retrosynthesis of the factor IIa‐binding domain (light grey) and the carbohydrate spacer (black) of hexadecasaccharide 2.
5. Scheme 17.3 Synthesis of key building blocks 29 and 9. (a) TMSOTf (cat.), CH₂Cl₂, −20 °C, 1 h, crystallization tert‐amyl alcohol, 85%; (b) H₂, Pd/C 10%, THF, 40 °C, 6 h; (c) DMS, KHCO₃, THF, RT, 16 h; (d) Ac₂O, Et₃N, DMAP (cat.), THF, RT, 2.5 h, crystallization iPrOH; (e) NH₂NH₂·AcOH, toluene/EtOH (1 : 2), 8 °C, 3.5 h, crystallization iPrOH, 75% (4 steps); (f) 2,3‐dihydropyrane, methanesulfonic acid, CH₂Cl₂, 20 °C, 0.5 h; (g) sodium azide, AcOBu, Et₃N, NMP/H₂O, 100 °C, 24 h; (h) DMS, sodium tert‐amylate, morpholine, 0–5 °C, 2 h; (i) HCl 36% in EtOH, RT, 6 h, 80%, 4 steps; (j) Ac₂O, DMAP, CH₂Cl₂, 0–100 °C, 6 h, α/β 1 : 4, crystallization EtOH, α/β 2:98, 78%; (k) PhSH, BF₃·OEt₂, toluene, RT, 1 h, crystallization EtOH, 90%; (l) MeONa (cat.), MeOH/CH₂Cl₂, 20 °C, 3 h, crude; (m) PhCH(OMe)₂, H₂SO₄, DMF, 65 °C, 3 h, crystallization CH₃CN, 78% (2 steps); (n) Ac₂O, DMAP, CH₂Cl₂, RT, 2.5 h, crystallization EtOH, 91%; (o) NBS, THF/H₂O, 3 °C, 2 h, crystallization, 90%; (p) Cl₃CCN, DBU, toluene, RT, 16 h, crude; (q) HCl, 5/1 CH₃CN/H₂O, 60 °C, 3 h; (r) Bz₂O, Et₃N, CH₂Cl₂, 20 °C, 5 h, 70% (2 steps); (s) TMSOTf (cat.), toluene, −20 °C, 1 h, 85%; (t) 1,3‐dibromo‐5,5‐dimethylhydantoin, triflic acid, 2 : 1 toluene/ CH₂Cl₂, −7 °C, 30 min, 90%; (u) (i) MeONa, MeOH/toluene; (ii) DMS, tert‐BuONa, NMP, RT, 1 h, quant.; (iii) HCl, 5/1 CH₃CN/H₂O, 60 °C, 5 h; (iv) Bz₂O, Et₃N, toluene/CH₂Cl₂, 20 °C, 4 h, 60% for 27, 57% for 28, (4 steps)); (v) (i) Ac₂O, AcONa, 100 °C, 6 h; (ii) C₆H₁₁SH, BF₃·OEt₂, toluene, 86% (2 steps); (w) (i) NIS, TfOH, dioxane/CH₂Cl₂, −20 °C, 1.25 h, crude; (ii) Ac₂O, TfOH, toluene, −30 °C, 5.5 h, crude; (iii) morpholine, toluene, 40 °C, 16 h, 68% (3 steps); (iv) CCl₃CN, DBU, RT, 16 h, crude.
6. Scheme 17.4 Synthesis of idrabiotaparinux (1) and hexadecasaccharide 2 (final steps). (a) 15, TBDMSOTf (cat.), CH₂Cl₂, MTBE, −30 °C, 30 min, crystallization acetone, 80% (2 steps); 29, TBDMSOTf (cat.), toluene, CH₂Cl₂, −50 °C, 1.5 h, crystallization MeOH, 65% (2 steps); (b) (i) LiOH, iPrOH, H₂O, 0 °C, 19 h, crystallization iPrOH, 90%; (ii) SO₃·pyridine, DMF, 30 °C, 15 h, precipitation iPrOH, quant.; (c) 32: H₂, 10% Pd/C, H₂O, RT, 2 h, quant.; 33: H₂, 10% Pd/C, H₂O/tert‐BuOH, 15 bar, RT, 3 h, quant.; (d) 40, H₂O, acetone, 16 h, precipitation EtOH, 75% (4 steps) (1); 40, DMF/H₂O, 72 h, precipitation iPrOH/MTBE, 67% (4 steps) (2).

Strategies and Applications in Carbohydrate Chemistry