Front cover 1
Editors 6
Preface 8
List of Contributors 12
Contents 14
CH 1 Separation and Quantification of Flavonoids 16
CONTENTS 16
1.1 INTRODUCTION 16
1.2 EXTRACTION 17
1.3 PREPARATIVE SEPARATION 1.3.1 PRELIMINARY PURIFICATION 18
1.3.2 PREPARATIVE METHODS 19
1.4 ANALYTICAL METHODS 24
1.4.1 SAMPLE PREPARATION 24
1.4.2 THIN-LAYER CHROMATOGRAPHY 25
1.4.3 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY 28
1.4.4 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY\u2013ULTRAVIOLET SPECTROPHOTOMETRY 31
1.4.5 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY\u2013MASS SPECTROMETRY 35
1.4.6 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY\u2013NUCLEAR MAGNETIC RESONANCE 39
1.4.7 CAPILLARY ELECTROPHORESIS 45
1.5 OUTLOOK 45
REFERENCES 47
CH 2 Spectroscopic Techniques Applied to Flavonoids 52
CONTENTS 52
2.1 INTRODUCTION 53
2.2 NMR SPECTROSCOPY 2.2.1 INTRODUCTION 55
2.2.2 NMR SOLVENTS 56
2.2.3 NMR EXPERIMENTS 57
2.2.4 SOLID-STATE NMR 64
2.2.5 LIQUID CHROMATOGRAPHY\u2013NMR 65
2.2.6 NMR DATA 67
2.3 MASS SPECTROMETRY 83
2.3.1 MS INSTRUMENTATION 99
2.3.2 COUPLED TECHNIQUES INVOLVING MASS SPECTROMETRY 106
2.3.3 STRUCTURAL INFORMATION 109
2.3.4 QUANTITATIVE CONSIDERATIONS 113
2.4 VIBRATIONAL SPECTROSCOPY (IR AND RAMAN) 115
2.4.1 115
2.4.2 117
2.4.3 TWO-DIMENSIONAL IR ANALYSIS 117
2.4.4 COUPLED TECHNIQUES INVOLVING VIBRATIONAL SPECTROSCOPY 118
2.4.5 NEAR-INFRARED SPECTROSCOPY 119
2.5 ULTRAVIOLET\u2013VISIBLE ABSORPTION SPECTROSCOPY 119
2.5.1 ONLINE UV ABSORPTION SPECTROSCOPY 120
2.5.2 UV\u2013VIS ABSORPTION SPECTROSCOPY 120
2.5.3 UV\u2013VIS ABSORPTION SPECTROSCOPY INVOLVING FLAVONOIDS 123
2.6 COLOR MEASUREMENTS USING COMMISSION INTERNATIONALE DE L\u2019ECLAIRAGE SPECIFICATIONS 124
2.6.1 COLORIMETRIC STUDIES 125
2.6.2 ANTHOCYANIN-BASED COLORS 130
2.7 CIRCULAR DICHROISM SPECTROSCOPY 130
2.7.1 DETERMINATION 131
2.7.2 CIRCULAR DICHROISM 132
2.8 X-RAY CRYSTALLOGRAPHY 132
2.8.1 X-RAY STUDIES 132
2.8.2 X-RAY STUDIES 133
REFERENCES 133
CH 3 Molecular Biology and Biotechnology of Flavonoid Biosynthesis 158
CONTENTS 158
3.1 THE SCOPE OF THE REVIEW 159
3.2 OVERVIEW OF FLAVONOID BIOSYNTHESIS 160
3.3 BIOSYNTHESIS OF FLAVONOID PRECURSORS 164
3.3.1 ACETYL-COA CARBOXYLASE 166
3.3.2 PHENYLALANINE AMMONIA LYASE 166
3.3.3 CINNAMATE 4-HYDROXYLASE 167
3.3.4 4-COUMARATE:COA LIGASE 168
3.3.5 MODIFICATION 169
3.4 FORMATION OF ANTHOCYANINS 169
3.4.1 CHALCONE SYNTHASE 169
3.4.2 CHALCONE ISOMERASE 170
3.4.3 FLAVANONE 3b-HYDROXYLASE 171
3.4.4 DIHYDROFLAVONOL 4-REDUCTASE 171
3.4.5 ANTHOCYANIDIN SYNTHASE 172
3.4.6 FORMATION 173
3.4.7 FORMATION 174
3.4.8 FLAVONOID 3\u2019-HYDROXYLASE 175
3.4.9 ANTHOCYANIN MODIFICATION ENZYMES 175
3.5 FORMATION OF PROANTHOCYANIDINS AND PHLOBAPHENES 179
3.5.1 LEUCOANTHOCYANIDIN REDUCTASE 180
3.5.2 ANTHOCYANIDIN REDUCTASE 180
3.5.3 PROANTHOCYANIDIN POLYMERIZATION 181
3.6 FORMATION OF FLAVONES AND FLAVONOLS 182
3.7 FLAVONE AND FLAVONOL MODIFICATION ENZYMES 183
3.7.1 FLAVONE 183
3.7.2 FLAVONE 184
3.7.3 FLAVONE 185
3.8 BIOSYNTHESIS OF 5-DEOXYFLAVONOIDS 186
3.9 BIOSYNTHESIS OF ISOFLAVONOIDS AND THEIR DERIVATIVES 186
3.9.1 2-HYDROXYISOFLAVANONE SYNTHASE 187
3.9.2 4\u2019-O-METHYLATION 187
3.9.3 ISOFLAVONE 2\u2019- 190
3.9.4 ISOFLAVONE REDUCTASE 191
3.9.5 VESTITONE REDUCTASE 191
3.9.6 PTEROCARPAN 6A-HYDROXYLASE 192
3.9.7 SAM:6A-HYDROXYMAACKIAIN 3-O-METHYLTRANSFERASE 192
3.9.8 PTEROCARPAN PRENYLTRANSFERASES 192
3.9.9 PRENYLPTEROCARPAN CYCLASES 192
3.9.10 ISOFLAVONOID GLUCOSYLTRANSFERASES 193
3.9.11 FLAVONOID 6-HYDROXYLASE 193
3.10 FORMATION OF AURONES 193
3.11 OTHER ACTIVITIES OF FLAVONOID BIOSYNTHESIS 194
3.12 VACUOLAR IMPORTATION OF FLAVONOIDS 195
3.13 ENZYME COMPLEXES AND METABOLIC CHANNELING 196
3.14 ASSIGNING ENZYME FUNCTION FROM DNA SEQUENCE OR RECOMBINANT PROTEINS 197
3.15 REGULATION OF FLAVONOID GENE TRANSCRIPTION 197
3.15.1 ENVIRONMENTAL REGULATION 198
3.15.2 REGULATION 200
3.15.3 REGULATION 203
3.15.4 REGULATION 204
3.16 GENETIC MODIFICATION OF FLAVONOID BIOSYNTHESIS 205
3.16.1 PREVENTING FLAVONOID PRODUCTION 205
3.16.2 REDIRECTING SUBSTRATE 211
3.16.3 INTRODUCING NOVEL FLAVONOID COMPOUNDS 211
3.16.4 MODULATING PATHWAY REGULATION 214
3.17 CONCLUDING COMMENTS 215
3.18 ACKNOWLEDGMENTS 216
REFERENCES 216
CH 4 Flavonoids in Foods 234
CONTENTS 234
4.1 INTRODUCTION 234
4.2 DATABASE DEVELOPMENT 4.2.1 DATABASE DEVELOPMENT 237
4.2.2 SELECTION 238
4.2.3 COLLATION 239
4.3 DATABASE OF FLAVONOIDS IN FOODS 243
4.3.1 FRUITS 253
4.3.2 VEGETABLES 253
4.3.3 BEVERAGES 254
4.3.4 MISCELLANEOUS FOODS 254
4.4 QUALITY AND COMPLETENESS OF FLAVONOID CONTENT DATA 255
4.4.1 FACTORS AFFECTING FLAVONOID CONTENT 255
4.5 ESTIMATED DIETARY FLAVONOID INTAKE 4.5.1 ESTIMATION 257
4.5.2 PREVIOUS ESTIMATIONS 257
4.5.3 ESTIMATION 259
4.5.4 COMPARISON 260
4.5.5 FUTURE REQUIREMENTS 261
4.6 CONCLUSIONS 261
4.7 ACKNOWLEDGMENTS 261
REFERENCES 263
APPENDIX 1 BOTANICAL NAMES 271
APPENDIX 2 REFERENCES USED 274
CH 5 Flavonoids in Wine 278
CONTENTS 278
5.1 INTRODUCTION 278
5.2 ANALYTICAL PROCEDURES 5.2.1 EXTRACTION 279
5.2.2 ANALYSIS 281
5.2.3 ANALYSIS 285
5.3 GRAPE FLAVONOIDS 5.3.1 STRUCTURE 288
5.3.2 IMPACT 290
5.4 EXTRACTION OF GRAPE FLAVONOIDS INTO THE WINE 292
5.5 REACTIONS OF FLAVONOIDS IN MUSTS AND WINES 293
5.5.1 REACTIVITY 301
5.5.2 ENZYMATIC REACTIONS 301
5.5.3 CHEMICAL REACTIONS 304
5.5.4 FACTORS CONTROLLING FLAVONOID REACTIONS 314
5.6 PHYSICOCHEMICAL AND ORGANOLEPTIC PROPERTIES OF GRAPE AND WINE FLAVONOIDS 5.6.1 IMPACT 316
5.6.2 IMPACT 319
REFERENCES 321
CH 6 Dietary Flavonoids and Health \u2014 Broadening the Perspective 334
CONTENTS 334
6.1 INTRODUCTION 335
6.2 THE DIVERSITY OF DIETARY PPT 336
6.3 THE INTAKE OF PPT 337
6.4 ABSORPTION OF PPT AND THE NATURE OF THE PLASMA METABOLITES 6.4.1 INTRODUCTION 339
6.4.2 FLAVANOLS, FLAVANOL GALLATES, 341
6.4.3 FLAVONOL GLYCOSIDES 341
6.4.4 FLAVONES 342
6.4.5 ISOFLAVONES 342
6.4.6 FLAVANONES 343
6.4.7 CHALCONES, DIHDYROCHALCONES, 343
6.4.8 ANTHOCYANINS 343
6.4.9 STILBENES 344
6.4.10 HYDROXYBENZOIC ACIDS, HYDROXYCINNAMIC ACIDS, 344
6.4.11 OLEUROPEIN, TYROSOL, 345
6.4.12 HYDROLYZABLE TANNINS 345
6.4.13 LIGNINS 345
6.4.14 DERIVED POLYPHENOLS 345
6.4.15 PERSON-TO-PERSON VARIATION 346
6.5 PPT METABOLITES IN TISSUES 6.5.1 PSEUDO-PHARMACOKINETIC 346
6.5.2 BINDING 349
6.5.3 EFFECTS 349
6.5.4 TRANSFORMATION 353
6.6 PPT PRIOR TO ABSORPTION 6.6.1 INTERACTION 354
6.6.2 MODULATION 355
6.6.3 MODULATION 356
6.7 SAFETY ASSESSMENT OF DIETARY PPT 356
6.8 CONCLUSIONS AND FUTURE RESEARCH REQUIREMENTS 358
REFERENCES 359
CH 7 Isoflavonoids and Human Health 386
CONTENTS 386
7.1 INTRODUCTION 386
7.2 ISOFLAVONOIDS: DIETARY SOURCES AND INTAKES, METABOLISM, AND BIOAVAILABILITY 7.2.1 DIETARY SOURCES 387
7.2.2 METABOLISM 389
7.3 ISOFLAVONOIDS AND CANCER PREVENTION 7.3.1 HORMONE-DEPENDENT CANCER PREVENTION 392
7.3.2 ESTROGENS 392
7.3.3 ESTROGEN RECEPTOR MEDIATED EVENTS 393
7.3.4 ANIMAL MODELS 393
7.3.5 MECHANISMS 394
7.3.6 CLINICAL STUDIES 396
7.4 PROTECTION BY ISOFLAVONOIDS AGAINST CARDIOVASCULAR DISEASE 7.4.1 CHOLESTEROL-LOWERING 397
7.4.2 ANTIOXIDANT ACTION 398
7.4.3 ARTERIAL FUNCTION 399
7.4.4 CELLULAR EFFECTS 400
7.5 PROTECTION BY ISOFLAVONOIDS AGAINST OSTEOPOROSIS, COGNITIVE DECLINE, AND MENOPAUSAL SYMPTOMS? 7.5.1 OSTEOPOROSIS 400
7.5.2 MENOPAUSAL SYMPTOMS 401
7.6 ISOFLAVONOIDS: POTENTIAL RISKS 401
7.7 ISOFLAVONOIDS AND HUMAN HEALTH: CONCLUSIONS 402
REFERENCES 403
CH 8 Flavonoid Functions in Plants 412
CONTENTS 412
8.1 INTRODUCTION 412
8.2 ANTHOCYANINS AND 3-DEOXYANTHOCYANINS 8.2.1 DEFENSE 413
8.2.2 PROTECTION 415
8.2.3 PHOTOPROTECTION 418
8.2.4 ANTIOXIDANT ACTIVITY 421
8.2.5 ANTHOCYANINS 423
8.3 COLORLESS FLAVONOIDS 8.3.1 STRESS PROTECTION 424
8.3.2 REPRODUCTION 427
8.3.3 SIGNALING \u2014 A ROLE 430
8.3.4 PROTECTION 438
8.4 CONCLUSIONS 439
REFERENCES 440
CH 9 Flavonoid\u2013Protein Interactions 458
CONTENTS 458
9.1 GENERAL CONSIDERATIONS 458
9.1.1 THE BIOLOGICAL SIGNIFICANCE 459
9.1.2 MOLECULAR INTERACTIONS RESPONSIBLE 460
9.1.3 SPECIFICITY 462
9.2 EXAMPLES OF FLAVONOID\u2013PROTEIN INTERACTIONS IN MAN 9.2.1 INTERACTIONS PRIOR 464
9.2.2 INTERACTIONS INVOLVED 466
9.2.3 INTERACTIONS POTENTIALLY INVOLVED 469
9.3 CONCLUSION AND PERSPECTIVES 478
REFERENCES 479
CH 10 The Anthocyanins 486
CONTENTS 486
10.1 INTRODUCTION 487
10.1.1 ANTHOCYANIN STRUCTURES 487
10.1.2 NUTRITIONAL SUPPLEMENTS \u2014 HEALTH ASPECTS 488
10.1.3 FOOD COLORANTS 488
10.1.4 MOLECULAR BIOLOGY, BIOSYNTHESIS, 489
10.1.5 ANALYTICAL METHODS 489
10.2 ANTHOCYANIN CHEMISTRY 10.2.1 GENERAL ASPECTS 490
10.2.2 ANTHOCYANIDINS 490
10.2.3 ANTHOCYANINS NOT BASED 495
10.2.4 GLYCOSIDES 495
10.2.5 ANTHOCYANINS 513
10.2.6 DIMERIC FLAVONOIDS INCLUDING 518
10.2.7 METALLOANTHOCYANINS 521
10.2.8 ANTHOCYANIN COLORS 523
10.3 ANTHOCYANIN PRODUCTION 10.3.1 CELL CULTURES 526
10.3.2 SYNTHESIS 528
10.4 ANTHOCYANIN LOCALIZATION IN PLANT CELLS 529
10.5 CHEMOTAXONOMIC PATTERNS 530
10.5.1 ALLIACEAE 531
10.5.2 CONVOLVULACEAE 533
10.5.3 CRUCIFERAE 533
10.5.4 GENTIANACEAE 533
10.5.5 GERANIACEAE 534
10.5.6 LABIATAE 534
10.5.7 LEGUMINOSAE 535
10.5.8 LILIACEAE 535
10.5.9 NYMPHAEACEAE 535
10.5.10 ORCHIDACEAE 537
10.5.11 RANUNCULACEAE 537
10.5.12 SOLANACEAE 537
REFERENCES 538
APPENDIX A 552
CH 11 Flavans and Proanthocyanidins 568
CONTENTS 568
11.1 INTRODUCTION 568
11.2 NOMENCLATURE 569
11.3 STRUCTURES AND DISTRIBUTION 570
11.3.1 FLAVANS, FLAVAN-3-OLS, FLAVAN-4-OLS, 570
11.3.2 PROANTHOCYANIDINS 583
11.3.3 NONPROANTHOCYANIDINS 602
11.3.4 COMPLEX TANNINS 608
11.3.5 MISCELLANEOUS 615
11.3.6 NMR 615
11.3.7 HPLC\u2013MS ANALYSIS 620
REFERENCES 621
CH 12 Flavones and Flavonols 632
CONTENTS 632
12.1 INTRODUCTION 633
12.2 ORGANIZATION OF THE TABLES 633
12.3 FLAVONES 634
12.4 FLAVONOLS 660
12.5 FLAVONES WITH OTHER SUBSTITUENTS 694
12.5.1 C-METHYLFLAVONES 694
12.5.2 METHYLENEDIOXYFLAVONES 707
12.5.3 C-PRENYLFLAVONES 707
12.5.4 O-PRENYLFLAVONES 708
12.5.5 PYRANOFLAVONES 708
12.5.6 FURANOFLAVONES 708
12.5.7 FURANO- 710
12.5.8 C-PRENYL- 710
12.5.9 C-LINKED AROMATIC- 711
12.5.10 TEPHROSIA FLAVONES 711
12.5.11 ARTOCARPUS FLAVONES 713
12.5.12 FLAVONE\u2013COUMARIN HYBRIDS 713
12.6 FLAVONOLS WITH OTHER SUBSTITUENTS 713
12.6.1 C-METHYLFLAVONOLS 713
12.6.2 METHYLENEDIOXYFLAVONOLS 714
12.6.3 C-PRENYLFLAVONOLS 715
12.6.4 O-PRENYLFLAVONOLS 724
12.6.5 PYRANOFLAVONOLS 724
12.6.6 FURANOFLAVONOLS 724
12.6.7 C-PRENYL- 726
12.6.8 FLAVONOLS 726
12.6.9 VARIOUS CYCLOFLAVONOLS 726
12.6.10 HYBRID STRUCTURES 726
12.6.11 FURANOFLAVONOLS 726
12.7 FLAVONE AND FLAVONOL ESTERS 727
12.8 CHLORINATED FLAVONOIDS 727
12.9 FLAVONOIDS OF HELMINTHOSTACHYS 729
12.10 COMMENTS ON DISTRIBUTION AND ACCUMULATION 729
REFERENCES 731
APPENDIX 752
CH 13 Flavone and Flavonol O-Glycosides 764
CONTENTS 764
13.1 INTRODUCTION 764
13.2 SEPARATION, PURIFICATION, AND IDENTIFICATION 766
13.3 NEW FLAVONE AND FLAVONOL O-GLYCOSIDES 766
13.3.1 MONOSACCHARIDES 766
13.3.2 DISACCHARIDES 775
13.3.3 TRISACCHARIDES 796
13.3.4 TETRASACCHARIDES 797
13.3.5 SULFATE CONJUGATES 798
13.3.6 ACYLATED DERIVATIVES 800
13.3.7 NEW FLAVONE GLYCOSIDES \u2014 FURTHER CONSIDERATIONS 801
13.3.8 NEW FLAVONOL GLYCOSIDES \u2014 FURTHER CONSIDERATIONS 802
13.3.9 GLYCOSIDES 802
13.4 DISTRIBUTION PATTERNS 803
REFERENCES 805
APPENDIX A CHECKLIST 823
APPENDIX B CHECKLIST 839
CH 14 C-Glycosylflavonoids 872
CONTENTS 872
14.1 NATURAL SOURCES AND SOME TAXONOMIC IMPLICATIONS 873
14.1.1 PLANT SPECIES RICH 873
14.1.2 C-GLYCOSYLFLAVONOIDS 873
14.2 NATURALLY OCCURRING C-GLYCOSYLFLAVONOIDS 882
14.2.1 MONO-C-GLYCOSYLFLAVONOIDS 882
14.2.2 DI- 882
14.2.3 O-GLYCOSYL-C-GLYCOSYLFLAVONOIDS 889
14.2.4 O-ACYL-C-GLYCOSYLFLAVONOIDS 901
14.3 SEPARATION AND IDENTIFICATION OF C-GLYCOSYLFLAVONOIDS 14.3.1 CAPILLARY ZONE ELECTROPHORESIS SEPARATION 901
14.3.2 HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SEPARATION 906
14.3.3 NEW POLYMERS 907
14.3.4 MASS SPECTROMETRY 907
14.3.5 NMR SPECTROSCOPY 908
14.4 SYNTHESIS OF C-GLYCOSYLFLAVONOIDS 911
14.4.1 O\u2013C GLYCOSIDE REARRANGEMENT 911
14.4.2 FRIES-TYPE REARRANGEMENT 911
14.4.3 VIA C-b-D-GLUCOPYRANOSYL 2,6-DIMETHOXYBENZENE 912
14.5 C-GLYCOSYLFLAVONOIDS AND VACUOLAR STORAGE 912
14.6 BIOLOGICAL PROPERTIES OF C-GLYCOSYLFLAVONOIDS 14.6.1 ANTIOXIDANT ACTIVITY 913
14.6.2 C-GLYCOSYLFLAVONOIDS 913
14.6.3 C-GLYCOSYLFLAVONOIDS 914
14.6.4 C-GLYCOSYLFLAVONOIDS 914
14.6.5 ANTIBACTERIAL ROLE 915
14.6.6 C-GLYCOSYLFLAVONOIDS 915
14.7 MANUFACTURE AND CULTIVATION PROCESS AND C-GLYCOSYLFLAVONOIDS 917
REFERENCES 918
CH 15 Flavanones and Dihydroflavonols 932
CONTENTS 932
15.1 GENERAL INTRODUCTION 933
15.2 FLAVANONES 15.2.1 SIMPLE FLAVANONES 935
15.2.2 ISOPRENYLATED FLAVANONES 939
15.2.3 COMPLEX FLAVANONES 958
15.2.4 FLAVANONE GLYCOSIDES 967
15.3 DIHYDROFLAVONOLS 15.3.1 DIHYDROFLAVONOL AGLYCONES 973
15.3.2 DIHYDROFLAVONOL GLYCOSIDES 980
15.4 ACKNOWLEDGMENTS 983
REFERENCES 983
APPENDIX 994
CH 16 Chalcones, Dihydrochalcones, and Aurones 1018
CONTENTS 1018
16.1 GENERAL INTRODUCTION 1018
16.1.1 NOMENCLATURE 1020
16.1.2 OVERVIEW 1021
16.2 CHALCONES 16.2.1 CHALCONES 1024
16.2.2 ISOPRENYLATED CHALCONES 1034
16.2.3 CHALCONE GLYCOSIDES 1037
16.2.4 CHALCONE DIMERS 1038
16.2.5 DIELS\u2013ALDER ADDUCTS 1045
16.2.6 CHALCONE CONJUGATES 1049
16.2.7 QUINOCHALCONES 1050
16.3 DIHYDROCHALCONES 16.3.1 DIHYDROCHALCONES 1053
16.3.2 ISOPRENYLATED DIHYDROCHALCONES 1058
16.3.3 DIHYDROCHALCONE GLYCOSIDES 1062
16.3.4 DIHYDROCHALCONE DIMERS 1062
16.3.5 BENZYLATED DIHYDROCHALCONES 1065
16.3.6 DIHYDROCHALCONE\u2013LIGNAN CONJUGATES 1065
16.4 AURONES 16.4.1 AURONES 1067
16.4.2 AURONE GLYCOSIDES 1068
16.4.3 AURONE 1070
REFERENCES 1073
APPENDIX A Index of Molecular Formulae 1085
APPENDIX B Checklist of Known Chalcones, Dihydrochalcones, and Aurones 1090
CH 17 Bi-, Tri-, Tetra-, Penta-, and Hexaflavonoids 1116
CONTENTS 1116
17.1 INTRODUCTION 1117
17.2 NOMENCLATURE 1117
17.3 STRUCTURE AND DISTRIBUTION 1118
17.3.1 BIFLAVONOIDS 1118
17.3.2 TRIFLAVONOIDS 1135
17.3.3 TETRAFLAVONOIDS 1137
17.3.4 PENTAFLAVONOIDS 1139
17.3.5 HEXAFLAVONOIDS 1139
REFERENCES 1139
Appendix \u2014 Checklist for Isoflavonoids 1149
REFERENCES 1200
Index 1214
Back cover 1254