Flavonoids: Chemistry, Biochemistry and Applications

Description

At an academic level too, although flavonoid structure elucidation is rapidly becoming a mature science thanks to technological advances, studies of their bioavailability and physiological activity in both animals and plants is likely to become the new frontier. Exciting advances in the understanding of this physiological activity will undoubtedly lead to the more widespread application of flavonoids in the improvement of human health and in crop quality. A major influence, especially in the latter, is likely to be brought about through skilful genetic manipulation of the flavonoid biosynthetic pathway. Cover Half Title Flavonoids: Chemistry, Biochemistry and Applications Copyright Editors Preface List of Contributors Contents 1. Separation and Quantification of Flavonoids CONTENTS 1.1 INTRODUCTION 1.2 EXTRACTION 1.3 PREPARATIVE SEPARATION 1.3.1 PRELIMINARY PURIFICATION 1.3.2 PREPARATIVE METHODS 1.4 ANALYTICAL METHODS 1.4.1 SAMPLE PREPARATION 1.4.2 THIN-LAYER CHROMATOGRAPHY 1.4.3 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY 1.4.4 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY–ULTRAVIOLET SPECTROPHOTOMETRY 1.4.5 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY–MASS SPECTROMETRY 1.4.6 HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY–NUCLEAR MAGNETIC RESONANCE 1.4.7 CAPILLARY ELECTROPHORESIS 1.5 OUTLOOK REFERENCES 2. Spectroscopic Techniques Applied to Flavonoids CONTENTS 2.1 INTRODUCTION 2.2 NMR SPECTROSCOPY 2.2.1 INTRODUCTION 2.2.2 NMR SOLVENTS 2.2.3 NMR EXPERIMENTS 2.2.4 SOLID-STATE NMR 2.2.5 LIQUID CHROMATOGRAPHY–NMR 2.2.6 NMR DATA 2.3 MASS SPECTROMETRY 2.3.1 MS INSTRUMENTATION 2.3.2 COUPLED TECHNIQUES INVOLVING MASS SPECTROMETRY 2.3.3 STRUCTURAL INFORMATION 2.3.4 QUANTITATIVE CONSIDERATIONS 2.4 VIBRATIONAL SPECTROSCOPY (IR AND RAMAN) 2.4.1 IR AND RAMAN SPECTROSCOPIC TECHNIQUES IN STUDIES OF FLAVONOID STRUCTURES 2.4.2 IR AND RAMAN SPECTROSCOPIC TECHNIQUES IN STUDIES OF COMPLEXES INVOLVING FLAVONOIDS 2.4.3 TWO-DIMENSIONAL IR ANALYSIS 2.4.4 COUPLED TECHNIQUES INVOLVING VIBRATIONAL SPECTROSCOPY 2.4.5 NEAR-INFRARED SPECTROSCOPY 2.5 ULTRAVIOLET–VISIBLE ABSORPTION SPECTROSCOPY 2.5.1 ONLINE UV ABSORPTION SPECTROSCOPY 2.5.2 UV–VIS ABSORPTION SPECTROSCOPY 2.5.3 UV–VIS ABSORPTION SPECTROSCOPY INVOLVING FLAVONOIDS 2.6 COLOR MEASUREMENTS USING COMMISSION INTERNATIONALE DE L’ECLAIRAGE SPECIFICATIONS 2.6.1 COLORIMETRIC STUDIES 2.6.2 ANTHOCYANIN-BASED COLORS 2.7 CIRCULAR DICHROISM SPECTROSCOPY 2.7.1 DETERMINATION 2.7.2 CIRCULAR DICHROISM 2.8 X-RAY CRYSTALLOGRAPHY 2.8.1 X-RAY STUDIES 2.8.2 X-RAY STUDIES REFERENCES 3. Molecular Biology and Biotechnology of Flavonoid Biosynthesis CONTENTS 3.1 THE SCOPE OF THE REVIEW 3.2 OVERVIEW OF FLAVONOID BIOSYNTHESIS 3.3 BIOSYNTHESIS OF FLAVONOID PRECURSORS 3.3.1 ACETYL-COA CARBOXYLASE 3.3.2 PHENYLALANINE AMMONIA LYASE 3.3.3 CINNAMATE 4-HYDROXYLASE 3.3.4 4-COUMARATE:COA LIGASE 3.3.5 MODIFICATION 3.4 FORMATION OF ANTHOCYANINS 3.4.1 CHALCONE SYNTHASE 3.4.2 CHALCONE ISOMERASE 3.4.3 FLAVANONE 3b-HYDROXYLASE 3.4.4 DIHYDROFLAVONOL 4-REDUCTASE 3.4.5 ANTHOCYANIDIN SYNTHASE 3.4.6 FORMATION 3.4.7 FORMATION 3.4.8 FLAVONOID 3’-HYDROXYLASE 3.4.9 ANTHOCYANIN MODIFICATION ENZYMES 3.5 FORMATION OF PROANTHOCYANIDINS AND PHLOBAPHENES 3.5.1 LEUCOANTHOCYANIDIN REDUCTASE 3.5.2 ANTHOCYANIDIN REDUCTASE 3.5.3 PROANTHOCYANIDIN POLYMERIZATION 3.6 FORMATION OF FLAVONES AND FLAVONOLS 3.7 FLAVONE AND FLAVONOL MODIFICATION ENZYMES 3.7.1 FLAVONE 3.7.2 FLAVONE 3.7.3 FLAVONE 3.8 BIOSYNTHESIS OF 5-DEOXYFLAVONOIDS 3.9 BIOSYNTHESIS OF ISOFLAVONOIDS AND THEIR DERIVATIVES 3.9.1 2-HYDROXYISOFLAVANONE SYNTHASE 3.9.2 4’-O-METHYLATION 3.9.3 ISOFLAVONE 2’- 3.9.4 ISOFLAVONE REDUCTASE 3.9.5 VESTITONE REDUCTASE 3.9.6 PTEROCARPAN 6A-HYDROXYLASE 3.9.7 SAM:6A-HYDROXYMAACKIAIN 3-O-METHYLTRANSFERASE 3.9.8 PTEROCARPAN PRENYLTRANSFERASES 3.9.9 PRENYLPTEROCARPAN CYCLASES 3.9.10 ISOFLAVONOID GLUCOSYLTRANSFERASES 3.9.11 FLAVONOID 6-HYDROXYLASE 3.10 FORMATION OF AURONES 3.11 OTHER ACTIVITIES OF FLAVONOID BIOSYNTHESIS 3.12 VACUOLAR IMPORTATION OF FLAVONOIDS 3.13 ENZYME COMPLEXES AND METABOLIC CHANNELING 3.14 ASSIGNING ENZYME FUNCTION FROM DNA SEQUENCE OR RECOMBINANT PROTEINS 3.15 REGULATION OF FLAVONOID GENE TRANSCRIPTION 3.15.1 ENVIRONMENTAL REGULATION 3.15.2 REGULATION 3.15.3 REGULATION 3.15.4 REGULATION 3.16 GENETIC MODIFICATION OF FLAVONOID BIOSYNTHESIS 3.16.1 PREVENTING FLAVONOID PRODUCTION 3.16.2 REDIRECTING SUBSTRATE 3.16.3 INTRODUCING NOVEL FLAVONOID COMPOUNDS 3.16.4 MODULATING PATHWAY REGULATION 3.17 CONCLUDING COMMENTS 3.18 ACKNOWLEDGMENTS REFERENCES 4. Flavonoids in Foods CONTENTS 4.1 INTRODUCTION 4.2 DATABASE DEVELOPMENT 4.2.1 DATABASE DEVELOPMENT 4.2.2 SELECTION 4.2.3 COLLATION 4.3 DATABASE OF FLAVONOIDS IN FOODS 4.3.1 FRUITS 4.3.2 VEGETABLES 4.3.3 BEVERAGES 4.3.4 MISCELLANEOUS FOODS 4.4 QUALITY AND COMPLETENESS OF FLAVONOID CONTENT DATA 4.4.1 FACTORS AFFECTING FLAVONOID CONTENT 4.5 ESTIMATED DIETARY FLAVONOID INTAKE 4.5.1 ESTIMATION 4.5.2 PREVIOUS ESTIMATIONS 4.5.3 ESTIMATION 4.5.4 COMPARISON 4.5.5 FUTURE REQUIREMENTS 4.6 CONCLUSIONS 4.7 ACKNOWLEDGMENTS REFERENCES APPENDIX 1 BOTANICAL NAMES APPENDIX 2 REFERENCES USED 5. Flavonoids in Wine CONTENTS 5.1 INTRODUCTION 5.2 ANALYTICAL PROCEDURES 5.2.1 EXTRACTION 5.2.2 ANALYSIS 5.2.3 ANALYSIS 5.3 GRAPE FLAVONOIDS 5.3.1 STRUCTURE 5.3.2 IMPACT 5.4 EXTRACTION OF GRAPE FLAVONOIDS INTO THE WINE 5.5 REACTIONS OF FLAVONOIDS IN MUSTS AND WINES 5.5.1 REACTIVITY 5.5.2 ENZYMATIC REACTIONS 5.5.3 CHEMICAL REACTIONS 5.5.4 FACTORS CONTROLLING FLAVONOID REACTIONS 5.6 PHYSICOCHEMICAL AND ORGANOLEPTIC PROPERTIES OF GRAPE AND WINE FLAVONOIDS 5.6.1 IMPACT 5.6.2 IMPACT REFERENCES 6. Dietary Flavonoids and Health — Broadening the Perspective CONTENTS 6.1 INTRODUCTION 6.2 THE DIVERSITY OF DIETARY PPT 6.3 THE INTAKE OF PPT 6.4 ABSORPTION OF PPT AND THE NATURE OF THE PLASMA METABOLITES 6.4.1 INTRODUCTION 6.4.2 FLAVANOLS, FLAVANOL GALLATES, 6.4.3 FLAVONOL GLYCOSIDES 6.4.4 FLAVONES 6.4.5 ISOFLAVONES 6.4.6 FLAVANONES 6.4.7 CHALCONES, DIHDYROCHALCONES, 6.4.8 ANTHOCYANINS 6.4.9 STILBENES 6.4.10 HYDROXYBENZOIC ACIDS, HYDROXYCINNAMIC ACIDS, 6.4.11 OLEUROPEIN, TYROSOL, 6.4.12 HYDROLYZABLE TANNINS 6.4.13 LIGNINS 6.4.14 DERIVED POLYPHENOLS 6.4.15 PERSON-TO-PERSON VARIATION 6.5 PPT METABOLITES IN TISSUES 6.5.1 PSEUDO-PHARMACOKINETIC 6.5.2 BINDING 6.5.3 EFFECTS 6.5.4 TRANSFORMATION 6.6 PPT PRIOR TO ABSORPTION 6.6.1 INTERACTION 6.6.2 MODULATION 6.6.3 MODULATION 6.7 SAFETY ASSESSMENT OF DIETARY PPT 6.8 CONCLUSIONS AND FUTURE RESEARCH REQUIREMENTS REFERENCES 7. Isoflavonoids and Human Health CONTENTS 7.1 INTRODUCTION 7.2 ISOFLAVONOIDS: DIETARY SOURCES AND INTAKES, METABOLISM, AND BIOAVAILABILITY 7.2.1 DIETARY SOURCES 7.2.2 METABOLISM 7.3 ISOFLAVONOIDS AND CANCER PREVENTION 7.3.1 HORMONE-DEPENDENT CANCER PREVENTION 7.3.2 ESTROGENS 7.3.3 ESTROGEN RECEPTOR MEDIATED EVENTS 7.3.4 ANIMAL MODELS 7.3.5 MECHANISMS 7.3.6 CLINICAL STUDIES 7.4 PROTECTION BY ISOFLAVONOIDS AGAINST CARDIOVASCULAR DISEASE 7.4.1 CHOLESTEROL-LOWERING 7.4.2 ANTIOXIDANT ACTION 7.4.3 ARTERIAL FUNCTION 7.4.4 CELLULAR EFFECTS 7.5 PROTECTION BY ISOFLAVONOIDS AGAINST OSTEOPOROSIS, COGNITIVE DECLINE, AND MENOPAUSAL SYMPTOMS? 7.5.1 OSTEOPOROSIS 7.5.2 MENOPAUSAL SYMPTOMS 7.6 ISOFLAVONOIDS: POTENTIAL RISKS 7.7 ISOFLAVONOIDS AND HUMAN HEALTH: CONCLUSIONS REFERENCES 8. Flavonoid Functions in Plants CONTENTS 8.1 INTRODUCTION 8.2 ANTHOCYANINS AND 3-DEOXYANTHOCYANINS 8.2.1 DEFENSE 8.2.2 PROTECTION 8.2.3 PHOTOPROTECTION 8.2.4 ANTIOXIDANT ACTIVITY 8.2.5 ANTHOCYANINS 8.3 COLORLESS FLAVONOIDS 8.3.1 STRESS PROTECTION 8.3.2 REPRODUCTION 8.3.3 SIGNALING — A ROLE 8.3.4 PROTECTION 8.4 CONCLUSIONS REFERENCES 9. Flavonoid–Protein Interactions CONTENTS 9.1 GENERAL CONSIDERATIONS 9.1.1 THE BIOLOGICAL SIGNIFICANCE 9.1.2 MOLECULAR INTERACTIONS RESPONSIBLE 9.1.3 SPECIFICITY 9.2 EXAMPLES OF FLAVONOID–PROTEIN INTERACTIONS IN MAN 9.2.1 INTERACTIONS PRIOR 9.2.2 INTERACTIONS INVOLVED 9.2.3 INTERACTIONS POTENTIALLY INVOLVED 9.3 CONCLUSION AND PERSPECTIVES REFERENCES 10. The Anthocyanins CONTENTS 10.1 INTRODUCTION 10.1.1 ANTHOCYANIN STRUCTURES 10.1.2 NUTRITIONAL SUPPLEMENTS — HEALTH ASPECTS 10.1.3 FOOD COLORANTS 10.1.4 MOLECULAR BIOLOGY, BIOSYNTHESIS, 10.1.5 ANALYTICAL METHODS 10.2 ANTHOCYANIN CHEMISTRY 10.2.1 GENERAL ASPECTS 10.2.2 ANTHOCYANIDINS 10.2.3 ANTHOCYANINS NOT BASED 10.2.4 GLYCOSIDES 10.2.5 ANTHOCYANINS 10.2.6 DIMERIC FLAVONOIDS INCLUDING 10.2.7 METALLOANTHOCYANINS 10.2.8 ANTHOCYANIN COLORS 10.3 ANTHOCYANIN PRODUCTION 10.3.1 CELL CULTURES 10.3.2 SYNTHESIS 10.4 ANTHOCYANIN LOCALIZATION IN PLANT CELLS 10.5 CHEMOTAXONOMIC PATTERNS 10.5.1 ALLIACEAE 10.5.2 CONVOLVULACEAE 10.5.3 CRUCIFERAE 10.5.4 GENTIANACEAE 10.5.5 GERANIACEAE 10.5.6 LABIATAE 10.5.7 LEGUMINOSAE 10.5.8 LILIACEAE 10.5.9 NYMPHAEACEAE 10.5.10 ORCHIDACEAE 10.5.11 RANUNCULACEAE 10.5.12 SOLANACEAE REFERENCES APPENDIX A 11. Flavans and Proanthocyanidins CONTENTS 11.1 INTRODUCTION 11.2 NOMENCLATURE 11.3 STRUCTURES AND DISTRIBUTION 11.3.1 FLAVANS, FLAVAN-3-OLS, FLAVAN-4-OLS, 11.3.2 PROANTHOCYANIDINS 11.3.3 NONPROANTHOCYANIDINS 11.3.4 COMPLEX TANNINS 11.3.5 MISCELLANEOUS 11.3.6 NMR 11.3.7 HPLC–MS ANALYSIS REFERENCES 12. Flavones and Flavonols CONTENTS 12.1 INTRODUCTION 12.2 ORGANIZATION OF THE TABLES 12.3 FLAVONES 12.4 FLAVONOLS 12.5 FLAVONES WITH OTHER SUBSTITUENTS 12.5.1 C-METHYLFLAVONES 12.5.2 METHYLENEDIOXYFLAVONES 12.5.3 C-PRENYLFLAVONES 12.5.4 O-PRENYLFLAVONES 12.5.5 PYRANOFLAVONES 12.5.6 FURANOFLAVONES 12.5.7 FURANO- 12.5.8 C-PRENYL- 12.5.9 C-LINKED AROMATIC- 12.5.10 TEPHROSIA FLAVONES 12.5.11 ARTOCARPUS FLAVONES 12.5.12 FLAVONE–COUMARIN HYBRIDS 12.6 FLAVONOLS WITH OTHER SUBSTITUENTS 12.6.1 C-METHYLFLAVONOLS 12.6.2 METHYLENEDIOXYFLAVONOLS 12.6.3 C-PRENYLFLAVONOLS 12.6.4 O-PRENYLFLAVONOLS 12.6.5 PYRANOFLAVONOLS 12.6.6 FURANOFLAVONOLS 12.6.7 C-PRENYL- 12.6.8 FLAVONOLS 12.6.9 VARIOUS CYCLOFLAVONOLS 12.6.10 HYBRID STRUCTURES 12.6.11 FURANOFLAVONOLS 12.7 FLAVONE AND FLAVONOL ESTERS 12.8 CHLORINATED FLAVONOIDS 12.9 FLAVONOIDS OF HELMINTHOSTACHYS 12.10 COMMENTS ON DISTRIBUTION AND ACCUMULATION REFERENCES APPENDIX 13. Flavone and Flavonol O-Glycosides CONTENTS 13.1 INTRODUCTION 13.2 SEPARATION, PURIFICATION, AND IDENTIFICATION 13.3 NEW FLAVONE AND FLAVONOL O-GLYCOSIDES 13.3.1 MONOSACCHARIDES 13.3.2 DISACCHARIDES 13.3.3 TRISACCHARIDES 13.3.4 TETRASACCHARIDES 13.3.5 SULFATE CONJUGATES 13.3.6 ACYLATED DERIVATIVES 13.3.7 NEW FLAVONE GLYCOSIDES — FURTHER CONSIDERATIONS 13.3.8 NEW FLAVONOL GLYCOSIDES — FURTHER CONSIDERATIONS 13.3.9 GLYCOSIDES 13.4 DISTRIBUTION PATTERNS REFERENCES APPENDIX A CHECKLIST APPENDIX B CHECKLIST 14. C-Glycosylflavonoids CONTENTS 14.1 NATURAL SOURCES AND SOME TAXONOMIC IMPLICATIONS 14.1.1 PLANT SPECIES RICH 14.1.2 C-GLYCOSYLFLAVONOIDS 14.2 NATURALLY OCCURRING C-GLYCOSYLFLAVONOIDS 14.2.1 MONO-C-GLYCOSYLFLAVONOIDS 14.2.2 DI- AND TRI-C-GLYCOSYLFLAVONOIDS 14.2.3 O-GLYCOSYL-C-GLYCOSYLFLAVONOIDS 14.2.4 O-ACYL-C-GLYCOSYLFLAVONOIDS 14.3 SEPARATION AND IDENTIFICATION OF C-GLYCOSYLFLAVONOIDS 14.3.1 CAPILLARY ZONE ELECTROPHORESIS SEPARATION 14.3.2 HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SEPARATION 14.3.3 NEW POLYMERS 14.3.4 MASS SPECTROMETRY 14.3.5 NMR SPECTROSCOPY 14.4 SYNTHESIS OF C-GLYCOSYLFLAVONOIDS 14.4.1 O–C GLYCOSIDE REARRANGEMENT 14.4.2 FRIES-TYPE REARRANGEMENT 14.4.3 VIA C-b-D-GLUCOPYRANOSYL 2,6-DIMETHOXYBENZENE 14.5 C-GLYCOSYLFLAVONOIDS AND VACUOLAR STORAGE 14.6 BIOLOGICAL PROPERTIES OF C-GLYCOSYLFLAVONOIDS 14.6.1 ANTIOXIDANT ACTIVITY OF C-GLYCOSYLFLAVONOIDS 14.6.2 C-GLYCOSYLFLAVONOIDS 14.6.3 C-GLYCOSYLFLAVONOIDS 14.6.4 C-GLYCOSYLFLAVONOIDS 14.6.5 ANTIBACTERIAL ROLE 14.6.6 C-GLYCOSYLFLAVONOIDS 14.7 MANUFACTURE AND CULTIVATION PROCESS AND C-GLYCOSYLFLAVONOIDS REFERENCES 15. Flavanones and Dihydroflavonols CONTENTS 15.1 GENERAL INTRODUCTION 15.2 FLAVANONES 15.2.1 SIMPLE FLAVONONES 15.2.2 ISOPRENYLATED FLAVANONES 15.2.3 COMPLEX FLAVANONES 15.2.4 FLAVANONE GLYCOSIDES 15.3 DIHYDROFLAVONOLS 15.3.1 DIHYDROFLAVONOL AGLYCONES 15.3.2 DIHYDROFLAVONOL GLYCOSIDES 15.4 ACKNOWLEDGMENTS REFERENCES APPENDIX 16. Chalcones, Dihydrochalcones, and Aurones CONTENTS 16.1 GENERAL INTRODUCTION 16.1.1 NOMENCLATURE 16.1.2 OVERVIEW 16.2 CHALCONES 16.2.1 CHALCONES 16.2.2 ISOPRENYLATED CHALCONES 16.2.3 CHALCONE GLYCOSIDES 16.2.4 CHALCONE DIMERS 16.2.5 DIELS–ALDER ADDUCTS 16.2.6 CHALCONE CONJUGATES 16.2.7 QUINOCHALCONES 16.3 DIHYDROCHALCONES 16.3.1 DIHYDROCHALCONES 16.3.2 ISOPRENYLATED DIHYDROCHALCONES 16.3.3 DIHYDROCHALCONE GLYCOSIDES 16.3.4 DIHYDROCHALCONE DIMERS 16.3.5 BENZYLATED DIHYDROCHALCONES 16.3.6 DIHYDROCHALCONE–LIGNAN CONJUGATES 16.4 AURONES 16.4.1 AURONES 16.4.2 AURONE GLYCOSIDES 16.4.3 AURONE REFERENCES APPENDIX A Index of Molecular Formulae APPENDIX B Checklist of Known Chalcones, Dihydrochalcones, and Aurones 17. Bi-, Tri-, Tetra-, Penta-, and Hexaflavonoids CONTENTS 17.1 INTRODUCTION 17.2 NOMENCLATURE 17.3 STRUCTURE AND DISTRIBUTION 17.3.1 BIFLAVONOIDS 17.3.2 TRIFLAVONOIDS 17.3.3 TETRAFLAVONOIDS 17.3.4 PENTAFLAVONOIDS 17.3.5 HEXAFLAVONOIDS REFERENCES Appendix — Checklist for Isoflavonoids REFERENCES Index Cover back