Chemistry and Biology of Ellagitannins: An Underestimated Class of Bioactive Plant Polyphenois

Contents......Page 14
Preface......Page 6
1.1 Old and New Concepts of Tannins.......Page 22
1.1.1 About the chemical stability of ellagitannins.......Page 23
1.1.2 Definition of ellagitannins in the narrow and wider senses......Page 24
1.1.3 Stereochemistry of ellagitannins.......Page 25
1.1.4 Condensation of dehydroellagitannins with other substances......Page 26
1.1.5 Accumulation of an ellagitannin of specific structure in a plant.......Page 28
1.3.1 Oxidative biological transformations from gallotannins to ellagitannins and dehydroellagitannins......Page 30
1.3.2 Regiospecificity of the HHDP group on the glucose core, and its correlation to plant families......Page 32
1.3.3.1 Occurrence of C-glycosidic tannins in plants......Page 33
1.3.4 Oligomerization of ellagitannins leading to pentamers......Page 35
1.3.4.1 Oligomers as main components in a plant species......Page 37
1.3.4.2 Oligomerization via oxidative C–O and C–C coupling modes......Page 38
1.3.4.2.1 The GOG- and GOGOG-type units......Page 39
1.3.4.2.2 The DOG and D(OG)2-type units......Page 40
1.3.4.2.3 The GOD-type unit......Page 44
1.3.5 Macrocyclic oligomers......Page 45
1.3.6.2 Hydrolysis of ellagitannin oligomers into monomers.......Page 47
1.4.1 Classification of hydrolyzable tannins based on the oxidation stages of their polyphenolic functions......Page 50
1.4.2 Correlation of the oxidation stages with Cronquist’s system of plant evolution......Page 53
1.4.3 Isolation of oxidized ellagitannin oligomers in specific plant orders......Page 55
1.5 Main Ellagitannin-Rich Medicinal Plants......Page 57
1.6.1 Reduction, stabilization and precipitation of other substances by tannins, and solubilization of precipitates by excess tannin......Page 60
1.6.3 Antioxidant activities......Page 61
1.7.1 Antiviral, antimicrobial and immunomodulatory activities......Page 64
1.7.2 Antitumor activities......Page 65
1.7.2.2 Inhibition of tumor promotion.......Page 66
1.7.4 Effects on liver functions and others.......Page 67
1.8 Bibliography......Page 68
2.1 Monomeric Ellagitannins......Page 76
2.1.1 Primary ellagitannins (HHDP esters)......Page 78
2.1.2 Dehydroellagitannins......Page 80
2.1.3 Modified dehydroellagitannins......Page 81
2.1.4 C-Glycosidic ellagitannins......Page 84
2.1.5 Complex tannins (hybrids bearing a flavan-3-ol moiety)......Page 85
2.2 Oligomeric Ellagitannins......Page 88
2.2.1 Oligomers linked with a dehydrodigalloyl group.......Page 90
2.2.2 Oligomers linked with valoneoyl and dehydrovaloneoyl groups......Page 93
2.2.4 C-Glycosidic ellagitannin oligomers.......Page 98
2.3 Chemotaxonomic Significance of Oligomeric Ellagitannins......Page 102
2.4.1 Variation of antibacterial effects according to bacterial species.......Page 104
2.4.2 Effects on Helicobacter pylori.......Page 105
2.4.3 Effects on antibiotic-resistant bacteria......Page 106
2.4.4 Effects on Leishmania donovani.......Page 107
2.5 Bibliography......Page 109
3.1 Introduction......Page 115
3.2 Principal Structures and Definitions.......Page 117
3.3 Gallic Acid, the Principal Phenolic Unit......Page 120
3.4 Biosynthesis of β-Glucogallin......Page 122
3.5 ‘Simple’ Galloylglucose Esters: the Route to Pentagalloylglucose......Page 123
3.6 The Side Route to Gallotannins......Page 127
3.7.1 Search for pentagalloylglucose oxidizing enzymes.......Page 128
3.7.3 Biosynthesis of a dimeric ellagitannin, cornusiin E.......Page 131
3.8 Conclusions and Perspectives.......Page 134
3.9 Bibliography......Page 136
4. Physicochemical Properties and Biomimetic Reactions of Ellagitannins......Page 140
4.1 Introduction......Page 141
4.2.1 Structures of ellagitannins and their water solubility......Page 142
4.2.2 Hydrophobic association of pentagalloylglucose and ellagitannins with co-existing compounds......Page 143
4.2.3 Self-association and biogenesis of dimeric ellagitannins......Page 150
4.3.1 Dehydroellagitannins and related compounds.......Page 152
4.3.2 Similarities and differences between the oxidative dimerization of the galloyl group and the pyrogallol-type catechin B-ring......Page 156
4.3.3 Reactions of dehydroellagitannins and biomimetic conversions.......Page 158
4.3.4 Application of the reactions of the DHHDP bisester......Page 161
4.3.5 Additional oxidation reactions of HHDP and related acyl groups......Page 164
4.4 Conclusion......Page 166
4.5 Bibliography......Page 167
5. Strategies for the Synthesis of Ellagitannins......Page 173
5.1 Introduction......Page 174
5.2 Strategies for the Synthesis of Ellagitannins.......Page 175
5.2.1.1 Total synthesis of sanguiin H-5......Page 177
5.2.1.2 Construction of a 2,3-bridged ellagitannin scaffold......Page 179
5.2.1.3 Total syntheses of (S)-configured ellagitannins praecoxin B and pterocaryanin C, and (R)- configured artificial ellagitannins mahtabin A and pariin M.......Page 180
5.2.2.1 Total synthesis of strictinin......Page 185
5.2.2.2 Total syntheses of gemin D and hippomanin A......Page 187
5.2.2.4 Synthesis of O-perbenzyllagerstannin C......Page 190
5.2.2.5 Tellimagrandin I and tellimagrandin II .......Page 194
5.2.2.5.1 Synthesis of O-permethyltellimagrandin I......Page 195
5.2.2.5.3 Total synthesis of tellimagrandin I .......Page 197
5.2.2.5.4 Total synthesis of tellimagrandin II......Page 199
5.2.2.6 Total synthesis of coriariin A, a dimeric ellagitannin.......Page 200
5.2.3.1 Synthesis of O-permethyl-α-pedunculagin......Page 202
5.2.3.2 Total synthesis of pedunculagin via the biaryl coupling strategy......Page 203
5.2.3.3 Total synthesis of pedunculagin via the double esterification strategy.......Page 205
5.2.4.1 Construction of a 2,4-bridged species......Page 207
5.2.5.1 Synthesis of O-permethylcorilagin......Page 209
5.4 Bibliography......Page 212
6.1 Immune Function: LPS, lipid A and TNFα.......Page 224
6.1.1 Lipid A......Page 225
6.1.1.1 Lipid A structure and chemistry.......Page 226
6.1.1.2 Role in disease.......Page 227
6.1.1.3 Impact on human health......Page 228
6.1.2 Lipoteichoic acid, peptidoglycan, and exotoxins......Page 229
6.1.3 TNFα.......Page 230
6.1.3.1 TNFα generated from LPS exposure: mediator of
septic shock......Page 231
6.1.3.2 Potential for anticancer therapy......Page 232
6.1.3.3 Monocyte response pathway......Page 235
6.1.3.4 Role of LPBP, CD14, Tlr4, and other proteins.......Page 237
6.1.4.1 LPS agonists.......Page 243
6.1.4.2 LPS antagonists.......Page 244
6.2.1 Anticancer activity......Page 253
6.2.1.1 Agrimoniin......Page 254
6.2.1.2 Coriariin A......Page 255
6.2.1.3 Other ellagitannins.......Page 256
6.2.2.1 Immunostimulation – IL-1β secretion......Page 259
6.2.2.2 Other ellagitannins.......Page 261
6.3.1 β-PGG, agrimoniin, and a model dimer analog of coriariin
A induce TNFα secretion from hPBMC’s......Page 264
6.3.2 Structure/activity profile of ellagitannins and gallotannins......Page 265
6.4.1 Use of CD-14 antibodies as a probe for the participation of
CD14 in tannin-stimulated TNFα release.......Page 267
6.4.2 Use of HeJ/OuJ mice as a probe for TLR-4 participation in
tannin-stimulated TNFα release.......Page 268
6.5 Ellagitannins as TNFα Secretion Inhibitors......Page 270
6.5.1 β-PGG as an LPS antagonist......Page 271
6.5.1.2 In vivo testing of live rats experiencing septic shock......Page 272
6.5.2 Dimeric gallotannin analogues as lipid A antagonists......Page 273
6.5.2.1 In vitro testing with hPBMC’s.......Page 274
6.5.2.2 In vivo testing with live rats......Page 276
6.6 Conclusion......Page 277
6.7 Bibliography......Page 278
7.1 Introduction......Page 294
7.2 How Relevant Are ETs in the Diet?.......Page 295
7.3 Do Ellagitannins and Ellagic Acid Show Biological Activity?......Page 296
7.4 Is the Analytical Methodology Ready for the Analysis of these Metabolites in vivo?......Page 301
7.5 Models to Study Bioavailability and Metabolism.......Page 302
7.5.2 In vitro cell lines to study uptake and metabolism.......Page 303
7.5.3 Animal models.......Page 304
7.5.4 Humans.......Page 306
7.6.1 Absorption of free EA.......Page 309
7.6.2 Intestinal microflora metabolism......Page 310
7.6.4 Tissue distribution......Page 311
7.8 Conclusion......Page 312
7.9 Bibliography......Page 314
8.1 Introduction......Page 319
8.2.1 Analytical methods .......Page 320
8.2.2 Fresh and processed berries......Page 323
8.2.4 Grape juice and wine.......Page 326
8.2.5 Oak-aged wine.......Page 327
8.3 Dietary Intake......Page 328
8.4.1 Antioxidant activity......Page 329
8.4.2 Inhibition of growth of human pathogenic microbes......Page 331
8.4.3 Inhibition of cancer cell growth......Page 332
8.4.4 Cancer prevention.......Page 334
8.5 Conclusions......Page 335
8.6 Bibliography......Page 336
9.1.1 Characteristic structural features and natural occurrence......Page 341
9.1.1.1 Oak and chestnut C-glycosidic ellagitannins.......Page 343
9.1.1.2 Complex C-glycosidic ellagitannins.......Page 345
9.1.2 Biogenetic construction – What’s known !?.......Page 348
9.2.1 Chemical reactivity dichotomy......Page 354
9.2.1.1 Refractory chemical behavior of castalagin.......Page 355
9.2.1.2 Diastereofacial differentiation of the vescalaginderived benzylic cation......Page 357
9.2.2 Hemisynthesis of flavano-ellagitannins – The acutissimins story.......Page 359
9.3.1 Occurrence of flavano-ellagitannins in red wine......Page 362
9.3.2 An example of a condensation reaction with a non-phenolic wine nucleophile.......Page 366
9.3.3.1 Anthocyanins and wine coloration – A few facts......Page 368
9.3.3.3 Anthocyano-ellagitannins and wine coloration.......Page 369
9.3.4.1 Oxygen in wines – A few facts.......Page 372
9.3.4.2 Oxidative conversion of acutissimin A into mongolicain A......Page 373
9.4 Conclusion and Perspectives.......Page 376
9.5 Bibliography......Page 379
Index......Page 388