| | Contents | |
| | | |
| |
| | Preface | XIII |
| | List of Contributors | XV |
| 1 | Bioactive Macrocyclic Peptides and Peptide Mimics
Rob M.J. Liskamp, Dirk T.S. Rijkers, and Saskia E. Bakker | 1 |
| 1.1 | Introduction | 1 |
| 1.2 | Selected Cyclic Peptides | 4 |
| 1.2.1 | Vancomycin | 4 |
| 1.2.2 | Lantibiotic: Nisin | 6 |
| 1.2.3 | Cyclosporin A | 10 |
| 1.2.4 | Cyclotheonamide A and B | 13 |
| 1.2.5 | cyclo RGD Peptides as  V 3 Antagonists | 16 |
| 1.2.6 | SH2 Domain-Binding Peptides | 19 |
| 1.3 | Conclusions | 22 |
| 1.4 | Experimental: Selected Procedures | 22 |
| 1.4.1 | Synthesis of Bicyclic Peptide 9: an Alkene-bridged Mimic of the Vancomycin C-D-E Cavity | 22 |
| 1.4.2 | Synthesis of Cyclic Peptide 14: an Alkyne-bridged Mimic of the Nisin A-Ring Fragment | 22 |
| | References | 25 |
| 2 | Macrocycles by Ring-closure Metathesis
Joëlle Prunet, Anderson Rouge dos Santos, and Jean-Pierre Férézou | 29 |
| 2.1 | Introduction | 29 |
| 2.2 | How to Cyclize? | 32 |
| 2.2.1 | A Thermodynamic versus Kinetic Issue | 32 |
| 2.2.2 | General Experimental Conditions | 34 |
| 2.2.3 | In.uence of Polar Complexing Groups | 35 |
| 2.2.3.1 | A Decisive Factor for Success | 35 |
| 2.2.3.2 | The Titanium Trick | 36 |
| 2.2.3.3 | A Particularly Favorable Case: The Template-Directed RCM | 37 |
| 2.2.4 | Chemoselectivity | 37 |
| 2.2.5 | Substrate ‘‘Tuning’’ | 38 |
| 2.2.5.1 | Configurational/Conformational Aspect | 38 |
| 2.2.5.2 | Influence of Functional Group Protection | 39 |
| 2.3 | Factors Influencing the Double-Bond Configuration | 39 |
| 2.3.1 | A Thermodynamic versus Kinetic Issue | 40 |
| 2.3.2 | General Experimental Conditions | 42 |
| 2.3.3 | Substrate ‘‘Tuning’’ | 42 |
| 2.3.4 | Solutions | 44 |
| 2.4 | Ene-yne M-RCM | 45 |
| 2.5 | Tandem Processes Involving M-RCM | 46 |
| 2.5.1 | Tandem CM/RCM | 47 |
| 2.5.2 | Tandem ROM/RCM | 47 |
| 2.5.3 | Tandem RCM/ROM/RCM | 48 |
| 2.5.4 | Ring-Expansion Metathesis | 48 |
| 2.5.5 | Other One-Pot Multistep Processes | 49 |
| 2.5.6 | M-RCM as Part of MCR Strategies | 50 |
| 2.6 | Representative Synthetic Applications | 50 |
| 2.6.1 | Salicylihalamides/Oximidines: Potent Antitumor Agents with Selective anti-V-ATPase Activity | 51 |
| 2.6.1.1 | Salicylihalamides: In.uence of the Catalyst | 52 |
| 2.6.1.2 | Salicylihalamides: In.uence of the Phenol Protecting Group | 53 |
| 2.6.1.3 | Salicylihalamides: In.uence of the Alcohol-Protecting Group at C13 | 54 |
| 2.6.1.4 | Salicylihalamides: In.uence of the Nature of the C15 Side Chain | 54 |
| 2.6.1.5 | Salicylihalamides: Miscellaneous | 55 |
| 2.6.1.6 | Oximidines: Use of Relay Ring-closing Metathesis | 55 |
| 2.6.2 | Radicicol-Type Macrolides: a Promising Family of Anticancer Resorcylides | 56 |
| 2.6.3 | Coleophomones: a Versatile Access to this Class of Complex Polycyclic Diterpenes | 58 |
| 2.6.4 | RCM in Supramolecular Chemistry | 59 |
| 2.7 | Conclusion and Perspectives | 62 |
| 2.8 | Experimental: Selected Procedures | 62 |
| 2.8.1 | Synthesis of Compound 3 with Catalyst S1 | 62 |
| 2.8.2 | Synthesis of Compound 6 with Catalyst G1 | 62 |
| 2.8.3 | Synthesis of Compound 8 with Catalyst G2 | 63 |
| 2.8.4 | Synthesis of Compound 16 (R=SiMe2tBu) with Catalyst G1/Ti(OiPr)4 | 63 |
| 2.8.5 | Synthesis of Compound 49 by RCAM | 63 |
| 2.8.6 | Synthesis of Compound 53 with G1 by ene-yne RCM | 63 |
| | References | 64 |
| 3 | Supramolecular Macrocycle Synthesis by H-bonding Assembly
Pablo Ballester and Javier de Mendoza | 69 |
| 3.1 | Introduction | 69 |
| 3.2 | Strategies to Build up Supramolecular Macrocycles Based on Hydrogen Bonds | 74 |
| 3.3 | Strategies to Build up Supramolecular Cavities and Capsules Based on Hydrogen Bonds | 90 |
| 3.4 | Summary and Outlook | 105 |
| 3.5 | Experimental: Selected Procedures | 106 |
| 3.5.1 | Solid State Formation of the Hexameric Capsule Derived from Pyrogallol[4]arene (50c) | 106 |
| 3.5.2 | Crystals of the Host-Guest Arrangement of 52@(50b)6 | 106 |
| | References | 108 |
| 4 | Cucurbit[n]urils
Wei-Hao Huang, Simin Liu, and Lyle Isaacs | 113 |
| 4.1 | Introduction | 113 |
| 4.1.1 | Synthesis and Structure of Cucurbit[6]uril and Decamethylcucurbit[5]uril | 113 |
| 4.1.2 | Molecular Recognition Properties of Cucurbit[6]uril | 114 |
| 4.2 | New Members of the Cucurbit[n]uril Family | 115 |
| 4.2.1 | Proposed Mechanism of Cucurbit[n]uril Formation | 115 |
| 4.2.2 | Synthesis and Structure of Cucurbit[n]uril Homologs (n = 5, 7, 8, 10) | 116 |
| 4.2.2.1 | Reaction Conducted Under Milder Conditions | 116 |
| 4.2.2.2 | CB[5] Can be Released from CB[10].CB[5] to Yield Free Cucurbit[10]uril | 117 |
| 4.3 | Applications of Members of the Cucurbit[n]uril Family | 118 |
| 4.3.1 | Preparation of Molecular Switches | 118 |
| 4.3.2 | Self-Assembled Dendrimers | 119 |
| 4.3.3 | Preparation of Molecular Machines | 119 |
| 4.3.4 | Preparation of Complex Self-Sorting Systems | 121 |
| 4.3.5 | Allosteric Control of the Conformation of a Calix[4]arene Inside CB[10] | 122 |
| 4.3.6 | As a Carrier of Anti-Cancer Agents | 123 |
| 4.4 | Experimental Support for the Proposed Mechanism of CB[n] Formation | 124 |
| 4.4.1 | S-shaped and C-shaped Methylene-bridged Glycoluril Dimers | 124 |
| 4.4.1.1 | Synthesis of Methylene-bridged Glycoluril Dimers | 124 |
| 4.4.1.2 | S- to C-shaped Isomerization of Methylene-bridged Glycoluril Dimers | 126 |
| 4.4.1.3 | Mechanism of S- to C-shaped Isomerization | 126 |
| 4.4.1.4 | Implications for the Synthesis of Cucurbit[n]uril Analogs and Derivatives | 128 |
| 4.4.2 | Building-Block Approach to Cucurbit[n]uril Analogs | 128 |
| 4.4.3 | Building-Block Approach to Cucurbit[n]uril Derivatives | 129 |
| 4.4.4 | Identi.cation and Isolation of Inverted Cucurbit[n]urils (n = 6, 7) | 130 |
| 4.5 | Direct Functionalization of Cucurbit[n]urils | 131 |
| 4.5.1 | Perhydroxylation and Further Derivatization of CB[5]–CB[8] | 131 |
| 4.5.2 | Multivalent Binding of Sugar-Decorated Vesicles to Lectins | 132 |
| 4.5.3 | Cucurbit[n]uril-based Artificial Ion Channels | 132 |
| 4.6 | Nor-Seco-Cucurbit[10]uril | 133 |
| 4.6.1 | Detection and Isolation of Nor-Seco-Cucurbit[10]uril | 134 |
| 4.6.2 | Molecular Recognition Properties of Nor-Seco-Cucurbit[10]uril | 134 |
| 4.7 | Summary and Conclusions | 135 |
| 4.8 | Experimental: Selected Procedures | 137 |
| 4.8.1 | Synthesis of Glycolurils | 137 |
| 4.8.2 | Synthesis and Separation of Cucurbit[n]urils | 138 |
| 4.8.3 | Synthesis of Nor-Seco-Cucurbit[10]uril | 140 |
| | References | 141 |
| 5 | Tetra-urea Calix[4]arenes – From Dimeric Capsules to Novel Catenanes and Rotaxanes
Ganna Podoprygorina and Volker Böhmer | 143 |
| 5.1 | Introduction | 143 |
| 5.2 | Basics of Tetra-urea Calix[4]arenes | 148 |
| 5.2.1 | Synthesis | 148 |
| 5.2.2 | Dimeric Capsules | 149 |
| 5.2.3 | Heterodimers | 151 |
| 5.2.4 | Symmetry Properties | 152 |
| 5.3 | Preorganization in Dimers of Tetra-urea Calix[4]arenes | 153 |
| 5.3.1 | General Considerations | 153 |
| 5.3.2 | First Attempts | 154 |
| 5.4 | Multimacrocycles | 155 |
| 5.4.1 | Template Synthesis of Multimacrocyclic Calix[4]arenes | 155 |
| 5.4.2 | Double Template Synthesis of Giant Macrocycles | 160 |
| 5.5 | Multiple Catenanes Based on Calix[4]arenes | 162 |
| 5.5.1 | General Considerations | 162 |
| 5.5.2 | Bis[2]catenanes | 163 |
| 5.5.3 | Towards Novel Topologies | 166 |
| 5.5.4 | Bis[3]catenanes and Cyclic [8]Catenanes | 168 |
| 5.6 | Multiple Rotaxanes | 170 |
| 5.7 | Self-sorting and Formation of Larger Assemblies | 172 |
| 5.8 | Conclusions and Outlook | 176 |
| 5.9 | Experimental: Selected Procedures | 177 |
| 5.9.1 | Synthesis of Tetra-urea 5 (Y = C5H11; m = 9) | 177 |
| 5.9.2 | Synthesis of Bisloop Tetra-urea 8 (Y = C5H11; n = 20) | 177 |
| 5.9.3 | Synthesis of Bis[2]catenane 12 (Y = C5H11; n = 20) | 177 |
| 5.9.4 | Synthesis of Tetra-urea 6a (Y = C5H11; m = 6) | 178 |
| 5.9.5 | Synthesis of Tetraloop Tetra-urea 9 (Y = C5H11; n = 14) | 178 |
| 5.9.6 | Synthesis of [8]Catenane 14 (Y = C5H11; n = 14) | 179 |
| | References | 180 |
| 6 | Shape-Persistent Macrocycles Based on Acetylenic Scaffolding
Amber L. Sadowy and Rik R. Tykwinski | 185 |
| 6.1 | Introduction | 185 |
| 6.1.1 | SPM Synthesis through Intermolecular Reactions | 186 |
| 6.1.2 | SPM Synthesis through Intramolecular Reactions | 190 |
| 6.2 | Supramolecular SPMs | 194 |
| 6.2.1 | SPMs as Components in Supramolecular Assemblies | 195 |
| 6.2.2 | SPMs in Host–Guest Systems | 203 |
| 6.2.3 | Aggregation and Surface Chemistry of SPMs | 208 |
| 6.2.3.1 | Aggregation of SPMs | 209 |
| 6.2.3.2 | Liquid-Crystalline SPMs | 215 |
| 6.2.3.3 | Adsorption of SPMs on Surfaces | 218 |
| 6.3 | Conclusions | 224 |
| 6.4 | Experimental: Selected Procedures | 224 |
| 6.4.1 | SPM 13: Pd-Catalyzed Cadiot–Chodkiewicz Conditions | 224 |
| 6.4.2 | SPM 19: Use of Aryltriazene as a Masking Group for Aryl Iodides | 224 |
| 6.4.3 | SPM 20: Eglinton Conditions | 225 |
| 6.4.4 | SPM 33: Hay Conditions | 225 |
| 6.4.5 | Pre-Catenane 56: Breslow Conditions | 225 |
| 6.4.6 | SPM 91: Schiff-base Condensation Conditions | 226 |
| 6.4.7 | Large-scale Synthesis of SPM 124 via an Alkyne Metathesis | 226 |
| | References | 228 |
| 7 | Supramolecular 3D Architectures by Metal-directed Assembly of Synthetic Macrocycles
Laura Pirondini and Enrico Dalcanale | 233 |
| 7.1 | Introduction | 233 |
| 7.2 | Coordination Cages | 234 |
| 7.2.1 | Dimeric Calixarene-based Coordination Cages | 235 |
| 7.2.2 | Cavitand-based Dimeric Coordination Cages | 236 |
| 7.2.2.1 | The Apical Functionalization Approach | 236 |
| 7.2.2.2 | Introduction of the Ligands as Bridging Units | 248 |
| 7.2.3 | Trimeric, Tetrameric, and Hexameric Coordination Cages | 252 |
| 7.2.4 | Self-assembly of Coordination Cages on Surfaces | 255 |
| 7.2.5 | Self-assembly of Multitopic Macrocyclic Complexes | 263 |
| 7.3 | Conclusion | 271 |
| 7.4 | Experimental: Selected Procedures | 272 |
| 7.4.1 | Tetrapicolyl-bridged Cavitand 31a | 272 |
| 7.4.2 | Tetracyano Cavitand 40 | 272 |
| 7.4.3 | AC-dibridged Tolylpyridyl Cavitand 35 | 272 |
| 7.4.4 | fac-Br(CO)3Re AC Ditopic Cavitand Complex 36 | 273 |
| 7.4.5 | Tetratopic Cavitand Complex 48 | 273 |
| | References | 274 |
| 8 | New Properties and Reactions in Self-assembled M6L4 Coordination Cages
Makoto Fujita and Michito Yoshizawa | 277 |
| 8.1 | Introduction | 277 |
| 8.2 | Self-assembly of Hollow Complexes | 278 |
| 8.2.1 | M6L4 Octahedral Complex | 280 |
| 8.2.2 | Large-scale Production of the M6L4 Complex | 280 |
| 8.3 | Inclusion Properties | 288 |
| 8.3.1 | Inclusion of Adamantane and Carborane | 288 |
| 8.3.2 | Inclusion Geometry | 289 |
| 8.3.3 | Bimolecular Recognition | 291 |
| 8.3.4 | Recognition of Bulky Guests | 293 |
| 8.3.5 | The Recognition of Azobenzene and Stilbene | 295 |
| 8.3.6 | Molecular Ice | 296 |
| 8.3.7 | Peptide Recognition | 297 |
| 8.4 | New Physical Properties | 299 |
| 8.4.1 | Redox Control of Ferrocene | 299 |
| 8.4.2 | Induction of Intermolecular Spin–spin Interaction | 299 |
| 8.5 | New Reactions | 301 |
| 8.5.1 | [2+2] Ole.n Photodimerization | 302 |
| 8.5.2 | Pairwise-selective Ole.n Photodimerization | 303 |
| 8.5.3 | Unusual [2+2] Photoaddition | 303 |
| 8.5.4 | Diels-Alder Reaction | 303 |
| 8.5.5 | Alkane Oxidation | 306 |
| 8.5.6 | Wacker Oxidation | 306 |
| 8.5.7 | Discrete Siloxane Synthesis | 308 |
| 8.6 | Conclusion | 308 |
| 8.7 | Experimental: Synthesis of M6L4 Cage 2 | 309 |
| | References | 309 |
| 9 | Anion-binding Macrocycles
Evgeny A. Katayev, Patricia J. Melfi, and Jonathan L. Sessler | 315 |
| 9.1 | Introduction | 315 |
| 9.2 | Ditopic Receptors and Receptors for Ion Pairs | 317 |
| 9.2.1 | Crown Complexes | 318 |
| 9.2.2 | Calixarenes | 321 |
| 9.2.3 | Cholapods | 325 |
| 9.2.4 | Pyrroles | 326 |
| 9.2.5 | Miscellaneous | 330 |
| 9.3 | Receptors with Different Binding Sites | 332 |
| 9.4 | Conclusions | 341 |
| 9.5 | Experimental: Selected Procedures | 342 |
| 9.5.1 | Macrocycle H2SO4.53 | 342 |
| 9.5.2 | Macrocycle 55 | 342 |
| | References | 343 |
| 10 | Rotaxane and Catenane Synthesis
James A. Wisner and Barry A. Blight | 349 |
| 10.1 | Introduction | 349 |
| 10.1.1 | General Comments | 349 |
| 10.2 | Macrocyclization Reactions Resulting in Interlocked Products | 351 |
| 10.2.1 | Williamson Ether Synthesis | 351 |
| 10.2.2 | Quaternization of Aromatic Amines (Menschutkin Reaction) | 351 |
| 10.2.3 | Condensation of Amines with Acid Chlorides | 354 |
| 10.2.4 | Oxidative Acetylide Coupling | 361 |
| 10.2.5 | Alkene Metathesis | 366 |
| 10.2.6 | Imine Formation/Reductive Amination | 374 |
| 10.2.7 | Metal-Ligand Coordination | 379 |
| 10.3 | Conclusions | 384 |
| 10.4 | Experimental: Selected Procedures | 384 |
| 10.4.1 | [2]Catenane 14 | 384 |
| 10.4.2 | [2]Catenane 25 | 386 |
| 10.4.3 | [2]Rotaxane 81 | 386 |
| 10.4.4 | [2]Catenane 118 | 386 |
| | References | 387 |
| | Index | 393 |
