Natural products phytochemistry botany and metabolism of alkaloids phenolics and terpenes 1

Natural Products Kishan Gopal Ramawat Jean-Michel Me´rillon Editors Natural Products Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes With 1569 Figures and 307 Tables Editors-in-Chief: Kishan Gopal Ramawat Botany Department, M.L Sukhadia University Udaipur 313001 India Jean-Michel Me´rillon Biological-Active Plant Substances Study Group University of Bordeaux Institute of Vine and Wine Sciences Villenave d’Ornon France ISBN 978-3-642-22143-9 ISBN 978-3-642-22144-6 (eBook) ISBN 978-3-642-22145-3 (Print and electronic bundle) DOI 10.1007/ 978-3-642-22144-6 Springer Heidelberg New York Dordrecht London Library of Congress Control Number: 2013934974 # Springer-Verlag Berlin Heidelberg 2013 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically forthe purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work Duplication of this publication or parts thereof is permitted only under the provisions ofthe Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer Permissions for use may be obtained through RightsLink at theCopyright Clearance Center Violations are liable to prosecution under the respective Copyright Law The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made The publisher makes no warranty, express or implied,with respect to the material contained herein Printed on acid-free paper Springer is part of Springer Science + Business Media (www.springer.com) Preface We are pleased to present a five volume treatise on “Natural products: phytochemistry, botany and metabolism” Natural products are as diverse as plant biodiversity and it was a herculean task to bring together several hundred leading scientists distributed all over the world to contribute in this project This five volumes work on Natural Products is reference work providing state-of-the-art knowledge composed by highly renowned scientists in their field The book is intended to serve the needs of graduate students, Ph.D scholars, researchers in the field of phytochemistry, botany, agricultural sciences, pharmacy, nutrition, biotechnology and, industrial scientists and those involved in marketing phytochemicals, plants and their extracts The present reference work will encompass the information about well established phytochemicals, biology and biotechnology of medicinal plants or their products, their biosynthesis, novel production strategies, demand and uses, metabolism and bioavailability This book is a work of tertiary literature containing digested knowledge in an easily accessible format Use of medicinal plants is as old as human civilization and continuous efforts are being made to explore new and old medicinal plants for novel bioactive molecules or to produce these products in high amounts through modern technologies About 200,000 natural products of plant origin are known and many more are being identified from higher plants and micro-organisms Some plants based drugs are used since centuries and there are not many alternatives for some natural drugs as cardiac glycosides or morphine Various facets of bioactive molecules have developed very rapidly in the last two decades particularly due to newer tools of isolation and identification as well as refined molecular techniques to establish the biological properties of isolated molecules This endeavour is to timely compile this vast data generated in recent past This is well reflected in 139 chapters running in over 4000 pages of text and vast literature cited in each chapter The readers will find comprehensive information on almost all bioactive molecules While planning this book our endeavour was to incorporate articles that cover the entire gamut of bioactive molecules of all the three major classes, viz., alkaloids, phenolics and terpenes Each volume is further divided into sections such as General Biology and Biotechnology; Classes - Occurrence, Biosynthesis, Structure and Chemistry, v vi Preface Distribution; Methods of Analysis; (para) Pharmacology and Bioavailability; and Nutraceuticals and Functional Foods (in phenolics) Some examples are sufficient to illustrate the spectrum of chapters in different sections such as: on alkaloids (Biotechnology and genetic engineering for alkaloid production, various classes of alkaloids e.g., Purine alkaloids, Ergot alkaloids, Terpenoid indole alkaloids, Pharmacological effects of ephedrine, Lycopodium alkaloids, Biological activities of pepper alkaloids, Neurotoxic alkaloids from cyanobacteria, Prevention of brain disorders by nicotine, Opioids and pain treatment, Ecological roles of alkaloids); on phenolics (Genetics of flavonoids, Functional foods: Genetics, metabolome and engineering, phytonutrient levels, Cocoa cultivation, directed breeding and polyphenolics, classes of phenolics, Polyphenols and anticancer activity, Tannins and anthocyanins of wine: phytochemistry and organoleptic properties, Polyphenols and beer quality, Wine polyphenols and vascular protective effects, Isoflavonoids and phytoestrogenic activity, Functional grapes, Potential neuroprotective actions of dietary flavonoids, Prospects of functional foods / nutraceuticals and markets), and on terpenes (Terpenes: Chemistry, biological role and therapeutic applications, Biotransformation of terpenoids and steroids, Production and genetic engineering of terpenoids production in plant cell cultures and organ cultures, Taxol-producing fungi, Metabolic engineering of isoprenoids biosynthesis, classes of terpenes, Cannabinoids: Chemistry and Medicine, Phytosterols: Beneficial effects, Ginsenosides: Biological activities, Ginkgolides and neuroprotective effects, Quassinoids: Anti-cancer and antimalarial activities, Phytoecdysteroids: phytochemistry and pharmacological activity, Brassinosteroids and their biological activity, and so on) These compounds exhibit various ecological functions, provide protection against attack by herbivores and microbes, and serve as attractants for pollinators and seed-dispersing agents Natural products are explored as sources of drugs, flavouring agents, fragrances and for a wide range of therapies Rapid progress has been made in recent years in understanding natural product accumulation and synthesis, and regulation and functions It is timely to bring this information together with contemporary advances in chemistry, plant biology, ecology, and pharmacology and metabolism of natural products in the form of a comprehensive treatise on natural products Because of the voluminous work for the treatise, this project was spread over almost two years, from concept to print We would like to acknowledge cooperation, patient and support of our contributors who have put their serious efforts to ensure the high scientific quality of this book with up to date information This work could not be completed without active support of Springer team who took pains in streamlining the production process We are particularly indebt to Drs Marion Hertel, Lydia Muller, Sylvia Blago and Simone Giesler for their continuous support from very inception of the project March 2013 K G Ramawat J.-M Me´rillon About the Editors Professor (Dr.) K G Ramawat, Former Professor & Head Botany Department, M.L Sukhadia University, Udaipur, India Professor K G Ramawat did his Ph.D (1978, Plant Biotechnology) from the University of Jodhpur, India and joined as faculty member in January 1979 He joined M.L.Sukhadia University as Associate Professor in 1991 and became Professor in 2001 He served as Head, Department of Botany (2001-2004, 2010-2012), In charge, Department of Biotechnology (2003-2004), member task force on medicinal and aromatic plants, Department of Biotechnology, Government of India, New Delhi (2002-2005) and co-ordinator UGC-DRS and DST-FIST programmes (2002-2012) He did his Post-doctoral at the University of Tours, France (1983-85) and subsequently worked as visiting professor at University of Tours (1991) and University of Bordeaux2, France (1995, 1999, 2003, 2006, 2010) He visited Poland under INSA-PAN academic exchange programme (2005) During last 38 years of his career, he has published more than 170 peer reviewed papers and articles He has edited books on Biotechnology of medicinal plants, secondary metabolites, Bioactive molecules, Herbal drugs, Plant defence: biological control, Desert plants; published by Science Publishers Inc, Enfield, USA and Springer Verlag, Germany His research on recalcitrant woody legume trees of desert (Prosopis, Zizyphus, Commiphora), production of useful metabolites vii viii About the Editors from woody plants (Comiphora, Pueraria) was funded by UGC, CSIR, ICAR, DBT and DST, New Delhi Works related to use of novel growth modulators and elicitors on the production of guggulsterones, stibenes and isoflvonoids are well cited He has supervised doctoral thesis of 25 students He is member of several academic bodies, associations and editorial boards of journals Professeur Jean-Michel Me´rillon, Directeur de l’EA 3675 (Groupe d’Etude des Substances Ve´ge´tales a` Activite´ Biologique + Polyphe´nols Biotech), Faculte´ de Pharmacie, Universite´ de Bordeaux, Institut des Sciences de la Vigne et du Vin, Villenave d’Ornon, France Professor J.M Me´rillon received his M.Pharma (1979) and Ph.D (1984) from the University of Tours in France He joined the University of Tours as assistant professor in 1981, became associate professor in 1987, and a full professor in 1993 at the faculty of Pharmacy, University of Bordeaux, France He is currently group leader of a “study group on biologically active plant substances” at the Institute of Vine and Wine Sciences, which comprises 25 scientists and research students His group has worked for many years on phenolic compounds from vine and wine, mainly complex stilbenes and their involvement in health He has supervised the doctoral theses of 18 students He has published more than 125 research papers in internationally recognized journals He has an H index of 29 according to the analysis of documents published between 1996 and 2013 He has co-edited four books on secondary metabolites and biotechnology (Science Publishers, USA; Springer, Germany) He is involved in developing teaching on plant biology, natural bioactive compounds and biotechnology He has traveled widely as a senior professor Scientists from several countries are working in his laboratory and his research is supported by funding from the Aquitaine Regional Government, the Ministry of Higher Education and Research, and various private companies He founded a technology transfer unit in 2004, Polyphenols Biotech, providing support for R&D programs for SMEs and major groups from the cosmetic, pharmaceutical, agricultural and health-nutrition sectors Contents Volume Part I Alkaloids: General Biology and Biotechnology 1 Microbial Production of Plant Benzylisoquinoline Alkaloids Eitaro Matsumura, Motoki Matsuda, Fumihiko Sato, and Hiromichi Minami Alkaloids of Marine Macroalgae Kasım Cemal G€ uven, Burak Coban, Ekrem Sezik, H€ useyin Erdugan, and Ferda Kaleag˘asıog˘lu 25 Neurotoxic Alkaloids from Cyanobacteria Ralf Kellmann, Olivier Ploux, and Brett A Neilan 39 Bioproduction of Terpenoid Indole Alkaloids from Catharanthus roseus Cell Cultures Lorena Almagro, Mariana Sottomayor, and Maria Angeles Pedren˜o 85 Bioactive Alkaloids from South American Psychotria and Related Rubiaceae He´lio Nitta Matsuura, Diogo Denardi Porto, and Arthur Germano Fett-Neto 119 Ecological Role of Alkaloids Shaily Goyal 149 Plant In Vitro Systems as Sources of Tropane Alkaloids Vasil Georgiev, Andrey Marchev, Strahil Berkov, and Atanas Pavlov 173 Biotechnology and Genetic Engineering for Alkaloid Production Smita Srivastava and Ashok Kumar Srivastava 213 Marine Pyrroloiminoquinone Alkaloids, Makaluvamines and Discorhabdins, and Marine Pyrrole-Imidazole Alkaloids Hiromichi Fujioka and Yasuyuki Kita 251 ix 56 Functional Foods: Genetics, Metabolome, and Engineering Phytonutrient Levels 1743 47 Lepiniec L, Debeaujon I, Routaboul JM, Baudry A, Pourcel L, Nesi N, Caboche M (2006) Genetics and biochemistry of seed flavonoids Annu Rev Plant Biol 57:405–430 48 Debeaujon I, Le´on-Kloosterziel KM, Koornneef M (2000) Influence of the testa on seed dormancy, germination, and longevity in Arabidopsis Plant Physiol 122:403–414 49 Wilson MF, Whelan CJ (1990) The evolution of fruit color in fleshy-fruited plants Am Nat 136:790–809 50 Sanoner P, Guyot S, Marnet N, Molle D, Drilleau JP (1999) Polyphenol profiles of French cider apple varieties (Malus domestica sp) J Agric Food Chem 47:4847–4853 51 Tohge T et al (2005) Functional genomics by integrated analysis of metabolome and transcriptome of Arabidopsis plants over-expressing an MYB transcription factor Plant J 42:218–235 52 Tohge T, Yonekura-Sakakibara K, Niida R, Watanabe-Takahashi A, Saito K (2007) Phytochemical genomics in Arabidopsis thaliana: a case study for functional identification of flavonoid biosynthesis genes Pure Appl Chem 79:811–823 53 Fraser PD, Enfissi EMA, Halket JM, Truesdale MR, Yu D, Gerrish C, Bramley PM (2007) Manipulation of phytoene levels in tomato fruit: effects on isoprenoids, plastids, and intermediary metabolism Plant Cell 19:3194–3211 54 Luo J, Butelli E, Hill L, Parr A, Niggeweg R, Bailey P, Weisshaar B, Martin C (2008) AtMYB12 regulates caffeoyl quinic acid and flavonol synthesis in tomato: expression in fruit results in very high levels of both types of polyphenol Plant J 56:316–326 55 Stracke R, Ishihara H, Barsch GHA, Mehrtens F, Niehaus K, Weisshaar B (2007) Differential regulation of closely related R2R3-MYB transcription factors controls flavonol accumulation in different parts of the Arabidopsis thaliana seedling Plant J 50:660–677 doi:10.1111/j.1365-313X.2007.03078.x 56 Yonekura-Sakakibara K, Tohge T, Niida R, Saito K (2007) Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics J Biol Chem 282:14932–14941 doi:10.1074/jbc.M611498200 57 Anterola AM, Lewis NG (2002) Trends in lignin modification: a comprehensive analysis of the effects of genetic manipulations/ mutations on lignification and vascular integrity Phytochemistry 61:221–294 58 Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007) Biotechnology of flavonoids and other phenylpropanoid-derived natural products Part I: chemical diversity, impacts on plant biology and human health Biotechnol J 2:1214–1234 59 Krieger CJ, Zhang P, Mueller LA, Wang A, Paley S et al (2004) MetaCyc: a multiorganism database of metabolic pathways and enzymes Nucleic Acids Res 32: D438–D442 60 Tanner GJ, Francki KT, Abrahams S, Watson JM, Larkin PJ, Ashton AR (2003) Proanthocyanidin biosynthesis in plants: purification of legume leucoanthocyanidin reductase and molecular cloning of its cDNA J Biol Chem 278:31647–31656 61 Tanaka Y, Filippa B (2006) Flower color In: Ainsworth C (ed) Flowering and its manipulation, vol 20 Blackwell, London, pp 201–239 62 Schijlen EGWM, de Vos CHR, Martens S, Jonker HH, Rosin FM, Molthoff JW, Tikunov YM, Angenent GC, van Tunen AJ, Bovy AG (2007) RNA interference silencing of chalcone synthase, the first step in the flavonoid biosynthesis pathway, leads to parthenocarpic tomato fruits Plant Physiol 144:1520–1530 63 Schijlen E, Ric de Vos CH, Jonker H, van den Broeck H, Molthoff J, van Tunen A et al (2006) Pathway engineering for healthy phytochemicals leading to the production of novel flavonoids in tomato fruit Plant Biotechnol J 4:433–444 64 Lunkenbein S, Coiner H, Ric de Vos CH, Schaart JC, Boone MJ, Krens FA et al (2006) Molecular characterization of a stable antisense chalcone synthase phenotype in strawberry (Fragaria x ananassa) J Agric Food Chem 54:2145–2153 1744 T Fatima et al 65 Lorenc-Kukula K, Amarowicz R, Oszmianski J, Doermann P, Starzycki M, Skala J, Z˙uk M, Kulma A, Szopa J (2005) Pleiotropic effect of phenolic compounds content increases in transgenic flax plant J Agric Food Chem 53:3685–3692 66 D’Introno A, Paradiso A, Scoditti E, D’Amico L, De Paolis A, Carluccio MA, Nicoletti I, DeGara L, Santino A, Giovinazzo G (2009) Antioxidant and anti-inflammatory properties of tomato fruits synthesizing different amounts of stilbenes Plant Biotechnol J 7:422–429 67 Giovinazzo G, D’Amico L, Paradiso A, Bollini R, Sparvoli F, DeGara L (2005) Antioxidant metabolite profiles in tomato fruit constitutively expressing the grapevine stilbene synthase gene Plant Biotechnol J 3:57–69 68 R€uhmann S, Treutter D, Fritsche S, Briviba K, Szankowski I (2006) Piceid (resveratrol glucoside) synthesis in stilbene synthase transgenic apple fruit J Agric Food Chem 54:4633–4640 69 Hanhineva K, Rogachev I, Kokko H, Mintz-Oron S, Venger I, Karenlampi S, Aharoni A (2008) Non-targeted analysis of spatial metabolite composition in strawberry (Fragaria x ananassa) flowers Phytochemistry 69:2463–2481 doi:10.1016/j.phytochem.2008.07.009 70 Shih CH, Chen Y, Wang M, Chu IK, Lo C (2008) Accumulation of isoflavone genistin in transgenic tomato plants overexpressing a soybean isoflavone synthase gene J Agric Food Chem 56:5655–5661 71 Muir SR, Collins GJ, Robinson S, Hughes S, Bovy A, De Vos CHR, van Tunen AJ, Verhoeyen ME (2001) Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols Nat Biotechnol 19:470–474 72 Lucaszewicz M, Matysiak-Kata I, Skala J, Fecka I, Cisowski W, Szopa J (2004) Antioxidant capacity manipulation in transgenic potato tuber by changes in phenolic compounds content J Agric Food Chem 52:1526–1533 73 Li H, Flachowsky H, Fischer T, Hanke MV, Forkmann G, Treutter D, Schwab W, Hoffmann T, Szankowski I (2007) Maize Lc transcription factor enhances biosynthesis of anthocyanins, distinct proanthocyanidins and phenylpropanoids in apple (Malus domestica Borkh) Planta 226:1243–1254 74 Furukawa T, Maekawa M, Oki T, Suda I, Iida S, Shimada H, Takamure I, K-i K (2007) The Rc and Rd genes are involved in proanthocyanidin synthesis in rice pericarp Plant J 49:91–102 75 Gong Z-Z, Yamagishi E, Yamazaki M, Saito K (1999) A constitutively expressed Myc-like gene involved in anthocyanin biosynthesis from Perilla frutescens: molecular characterization, heterologous expression in transgenic plants and transactivation in yeast cells Plant Mol Biol 41:33–44 76 Mooney M, Desnos T, Harrison K, Jones J, Carpenter R, Coen E (1995) Altered regulation of tomato and tobacco pigmentation genes caused by the delila gene of Antirrhinum Plant J 7:333–339 77 Butelli E, Titta L, Giorgio M, Mock H-P, Matros A, Peterek S, Schijlen EGWM, Hall RD, Bovy AG, Luo J, Martin C (2008) Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors Nat Biotechnol 26:1301–1308 78 Adato A, Mandel T, Mintz-Oron S, Venger I, Levy D, Yativ M, Domı´nguez E, Wang Z, De Vos RCH, Jetter R, Schreiber L, Heredia A, Rogachev I, Aharoni A (2009) Fruit-surface flavonoid accumulation in tomato is controlled by a SlMYB12-regulated transcriptional network PLoS Genet 5:e1000777 79 Bovy A, de Vos R, Kemper M, Schijlen E, Almenar Pertejo M, Muir S, Collins G, Robinson S, Verhoeyen M, Hughes S, Santos-Buelga C, van Tunen A (2002) High-flavonol tomatoes resulting from the heterologous expression of the maize transcription factor genes LC and C1 Plant Cell 14:2509–2526 80 Mathews H, Clendennen SK, Caldwell CG, Liu XL, Connors K, Matheis N, Schuster DK, Menasco DJ, Wagoner W, Lightner J, Wagner DR (2003) Activation tagging in tomato identifies a transcriptional regulator of anthocyanin biosynthesis, modification, and transport Plant Cell 15:1689–1703 56 Functional Foods: Genetics, Metabolome, and Engineering Phytonutrient Levels 1745 81 Itkin M, Seybold H, Breitel D, Rogachev I, Meir S, Aharoni A (2009) TOMATO AGAMOUS-LIKE is a component of the fruit ripening regulatory network Plant J 60:1081–1095 82 Wang S, Liu J, Feng Y, Niu X, Giovannoni J, Liu Y (2008) Altered plastid levels and potential for improved fruit nutrient content by downregulation of the tomato DDB1-interacting protein CUL4 Plant J 55:89–103 83 Ververidis F, Trantas E, Douglas C, Vollmer G, Kretzschmar G, Panopoulos N (2007) Biotechnology of flavonoids and other phenylpropanoid-derived natural products Part II: Reconstruction of multienzyme pathways in plants and microbes Biotechnol J 2:1235–1249 84 Zuk M, Kulma A, Dyminska L, Szoltysek K, Prescha A, Hanuza J, Szopa J (2011) Flavonoid engineering of flax potentiate its biotechnological application BMC Biotechnol 11:10 85 Crozier A, Lean MEJ, McDonald MS, Black C (1997) Quantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce, and celery J Agric Food Chem 45:590–595 86 Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid Nat Biotechnol 22:746–754 87 Giliberto L, Perrotta G, Pallara P, Weller JL, Fraser PD, Bramley PM, Fiore A, Tavazza M, Giuliano G (2005) Manipulation of the blue light photoreceptor cryptochrome in tomato affects vegetative development, flowering time, and fruit antioxidant content Plant Physiol 137:199–208 88 Ingrosso I, Bonsegna S, De Domenico S, Laddomada B, Blando F, Santino A, Giovinazzo G (2011) Over-expression of a grape stilbene synthase gene in tomato induces parthenocarpy and causes abnormal pollen development Plant Physiol Biochem 49:1092–1099 89 Rotino GL, Perri E, Zottini M, Sommer H, Spena A (1997) Genetic engineering of parthenocarpic plants Nat Biotechnol 15:1398–1401 90 Ficcadenti N, Sestili S, Pandolfini T, Cirillo C, Rotino GL, Spena A (1999) Genetic engineering of parthenocarpic fruit development in tomato Mol Breeding 5:463–470 91 Pandolfini T, Rotino G, Camerini S, Defez R, Spena A (2002) Optimisation of transgene action at the post-transcriptional level: high quality parthenocarpic fruits in industrial tomatoes BMC Biotechnol 2:1 92 Davuluri GR, van Tuinen A, Fraser PD, Manfredonia A, Newman R, Burgess D, Brummell DA, King SR, Palys J, Uhlig J, Bramley PM, Pennings HMJ, Bowler C (2005) Fruit-specific RNAi-mediated suppression of DET1 enhances tomato nutritional quality Nat Biotechnol 7:825–826 93 Le Gall G, Colquhoun IJ, Davis AL, Collins GJ, Verhoeyen ME (2003) Metabolite profiling of tomato (Lycopersicon esculentum) using 1H NMR spectroscopy as a tool to detect potential unintended effects following a genetic modification J Agric Food Chem 51:2447–2456 94 Schreiber G, Reuveni M, Evenor D, Oren-Shamir M, Ovadia R, Sapir-Mir M, Bootbool-Man A, Nahon S, Shlomo H, Chen L, Levin I (2012) ANTHOCYANIN1 from Solanum chilense is more efficient in accumulating anthocyanin metabolites than its Solanum lycopersicum counterpart in association with the ANTHOCYANIN FRUIT phenotype of tomato Theor Appl Genetic 124:295–307 95 International Agency for Research on Cancer (1998) IARC handbooks of cancer prevention: carotenoids International Agency for Research on Cancer, Lyon 96 Institute of Medicine, Food and Nutrition Board (2000) Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids National Academy Press, Washington, DC, pp 325–400 97 van Het Hof KH, West CE, Weststrate JA, Hautvast JG (2000) Dietary factors that affect the bioavailability of carotenoids J Nutr 130:503–506 98 Yeum KJ, Russell RM (2002) Carotenoid bioavailability and bioconversion Annu Rev Nutr 22:483–504 1746 T Fatima et al 99 Gartner C, Stahl W, Sies H (1997) Lycopene is more bioavailable from tomato paste than from fresh tomatoes Am J Clin Nutr 66:116–122 100 Stahl W, Sies H (1992) Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans J Nutr 122:2161–2166 101 Handa AK, Anwar R, Mattoo AK (2013) Biotechnology of fruit quality In: Nath P, Bouzayen M, Mattoo AK, Pech J-C (eds) Fruit ripening: physiology, signalling and genomics CABI, Oxfordshire 102 Klee HJ, Giovannoni JJ (2011) Genetics and control of tomato fruit ripening and quality attributes Annu Rev Genetic 45:41–59 103 Rodrı´guez-Concepcio´n M (2010) Supply of precursors for carotenoid biosynthesis in plants Arch Biochem Biophys 504:118–122 104 Bian W, Barsan C, Egea I, Purgatto E et al (2011) Metabolic and molecular events occurring during chromoplast biogenesis J Botany doi:10.1155/2011/289859 105 Edwards RA, Reuter FH (1967) Pigment changes during the maturation of tomato fruits Food Technol Australia 19:352–357 106 Johjima T, Matsuzoe N (1995) Relationship between colour value and coloured carotenes content in fruit of various tomato cultivars and breeding lines Acta Hort 412:152–159 107 Mehta RA, Cassol T, Li N, Ali N, Handa AK, Mattoo AK (2002) Engineered polyamine accumulation in tomato enhances phytonutrient content, juice quality and vine life Nat Biotechnol 20:613–618 108 Ye X, Al-Babili S, Kl€ oti A, Zhang J, Lucca P, Beyer P, Potrykus I (2000) Engineering the provitamin A (b-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm Science 287:303–305 109 Beyer P, Al-Babili S, Ye X, Lucca P, Schaub P, Welsch R, Potrykus I (2002) Golden rice: Introducing the b-carotene biosynthesis pathway into rice endosperm by genetic engineering to defeat vitamin A deficiency Am Soc Nutr Sci 32:506S–510S 110 Mattoo AK, Sobolev AP, Neelam A, Goyal RK, Handa AK, Segre AL (2006) NMR spectroscopy-based metabolite profiles of transgenic tomato fruit engineered to accumulate polyamines spermidine and spermine reveal enhanced anabolic and nitrogen-carbon interactions Plant Physiol 142:1759–1770 111 Enfissi EMA, Fraser PD, Lois L-M, Boronat A, Schuch W, Bramley PM (2005) Metabolic engineering of the mevalonate and non-mevalonate isopentenyl diphosphate-forming pathways for the production of health-promoting isoprenoids in tomato Plant Biotechnol J 3:17–27 112 Morris WL, Ducreux L, Griffiths DW, Stewart D, Davies HV et al (2004) Carotenogenesis during tuber development and storage in potato J Exp Bot 55:975–982 113 Fraser PD, R€omer S, Shipton CA, Mills PM, Kiano JW, Misawa N, Drake RG, Schuch W, Bramley PM (2002) Biochemical evaluation of transgenic tomato plants expressing an addition phytoene synthase in a fruit-specific manner Proc Natl Acad Sci USA 99:1092–1097 114 R€omer S, Fraser PD, Kiano JW, Shipton CA, Misawa N, Schuch W, Bramley PM (2000) Elevation of the provitamin A content of transgenic tomato plants Nat Biotechnol 18:666–669 115 Burkhardt PK, Beyer P, W€ unn J, Kl€ oti A, Armstrong GA, Schledz M, von Lintig J, Potrykus I (1997) Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of provitamin A biosynthesis Plant J 11:1071–1078 116 Ducreux LJ, Morris WL, Hedley PE, Shepherd T, Davies HV, Millam S, Taylor MA (2005) Metabolic engineering of high carotenoid potato tubers containing enhanced levels of b-carotene and lutein J Exp Bot 56:81–89 117 Diretto G, Al-Babili S, Tavazza R, Papacchiolli V, Beyer P, Giuliano G (2007) Metabolic engineering of potato carotenoid content through tuber-specific overexpression of a bacterial mini-pathway PLoS One 2:e350 doi:10.1371/journal.pone.0000350 56 Functional Foods: Genetics, Metabolome, and Engineering Phytonutrient Levels 1747 118 Aluru M, Xu Y, Guo R, Wang Z, Li S, White W, Wang K, Rodermal S (2008) Generation of transgenic maize with enhanced provitamin A content J Exp Bot 59:3551–3562 119 Gerjets T, Sandmann G (2006) Ketocarotenoid formation in transgenic potato J Exp Bot 57:3639–3645 120 Yu B, Lydiate D, Young L, Sch€afer U, Hannoufa A (2008) Enhancing the carotenoid content of Brassica napus seeds by downregulating lycopene epsilon cyclase Transgenic Res 17:573–585 121 Fujisawa M, Watanabe M, Choi S-K, Teramoto M, Ohyama K, Misawa N (2008) Enrichment of carotenoids in flaxseed (Linum usitatissimum) by metabolic engineering with introduction of bacterial phytoene synthase gene crtB J Biosci Bioeng 105:636–641 122 Shewmaker CK, Sheehy JA, Daley M, Colburn S, Ke DY (1999) Seed-specific over-expression of phytoene synthase: increase in carotenoids and other metabolic effects Plant J 20:401–412 123 Ravanello MP, Ke D, Alvarez J, Huang B, Shewmaker CK (2003) Coordinate expression of multiple bacterial carotenoid genes in canola leading to altered carotenoid production Metab Eng 5:255–263 124 Wei S, Li X, Gruber MY, Li R, Zhou R, Zebarjadi A, Hannoufa A (2009) RNAi-mediated suppression of DET1 alters the levels of carotenoids and sinapate esters in seeds of Brassica napus J Agric Food Chem 57:5326–5333 125 Jayraj J, Devlin R, Punja Z (2008) Metabolic engineering of novel ketocarotenoid production in carrot plants Transgenic Res 17:489–501 126 Ronen G, Carmel-Goren L, Zamir D, Hirschberg J (2000) An alternative pathway to b-carotene formation in plant chromoplasts discovered by map-based cloning of Beta and old-gold color mutations in tomato Proc Natl Acad Sci USA 97:11102–11107 127 D’Ambrosio G, Griorio G, Marino I, Merendino A, Petrozza A, Salfi L, Stigliani AL, Cellini F (2004) Virtually complete conversion of lycopene into b-carotene in fruits of tomato plants transformed with the tomato lycopene b-cyclase (tlcy-b) cDNA Plant Sci 166:207–214 128 Rosati C, Aquilani R, Dharmapuri S, Pallara P, Marusic C, Tavazza R, Bouvier F, Camara B, Giuliano G (2000) Metabolic engineering of beta carotene and lycopene content in tomato fruit Plant J 24:413–419 129 Guo F, Zhou W, Zhang J, Xu Q, Deng X (2012) Effect of the citrus lycopene b-cyclase transgene on carotenoid metabolism in transgenic tomato fruits PLoS One 7:e32221 130 Wurbs D, Ruf S, Bock R (2007) Contained metabolic engineering in tomatoes by expression of carotenoid biosynthesis genes from the plastid genome Plant J 49:276–288 131 Dharmapuri S, Rosati C, Pallara P, Aquilani R, Bouvier F, Camara B, Giuliano G (2002) Metabolic engineering of xanthophyll content in tomato fruits FEBS Lett 519:30–34 132 Sun L, Yuan B, Zhang M, Wang L, Cui M, Wang Q, Leng P (2012) Fruit-specific RNAi-mediated suppression of SlNCED1 increases both lycopene and b-carotene contents in tomato fruit J Exp Bot 63:3097–3108 133 Lu S, Van Eck J, Zhou X, Lopez AB, O’Halloran DM et al (2006) The cauliflower Or gene encodes a DnaJ cysteine-rich domain-containing protein that mediates high-levels of beta-carotene accumulation Plant Cell 18:3594–3605 134 Lopez AB, Van Eck J, Conlin BJ, Paolillo DJ, O’Neill J, Li L (2008) Effect of the cauliflower OR transgene on carotenoid accumulation and chromoplast formation in transgenic potato tubers J Exp Bot 59:213–223 135 Nambeesan S, Datsenka T, Ferruzzi MG, Malladi A, Mattoo AK, Handa AK (2010) Overexpression of yeast spermidine synthase impacts ripening, senescence and decay symptoms in tomato Plant J 63:836–847 136 Neily MH, Matsukura C, Maucourt M, Bernillon S, Deborde C, Moing A, Yin Y-G, Saito T, Mori K, Asamizu E, Rolin D, Moriguchi T, Ezura H (2011) Enhanced polyamine accumulation alters carotenoid metabolism at the transcriptional level in tomato fruit over-expressing spermidine synthase J Plant Physiol 168:242–252 1748 T Fatima et al 137 Bassie L, Zhu C, Romagosa I, Christou P, Capell T (2008) Transgenic wheat plants expressing an oat arginine decarboxylase cDNA exhibit increases in polyamine content in vegetative tissue and seeds Mol Breeding 22:39–50 138 Fujisawa M, Misawa N (2010) Enrichment of carotenoids in flaxseed by introducing a bacterial phytoene synthase gene In: Fett-Neto AG (ed) Plant secondary metabolism engineering: methods and applications Springer, New York, pp 201–211 139 Galpaz N, Wang Q, Menda N, Zamir D, Hirschberg J (2008) Abscisic acid deficiency in the tomato mutant high-pigment leading to increased plastid number and higher fruit lycopene content Plant J 53:717–730 140 Food and Nutrition Board, Institute of Medicine (2002) Dietary fats: total fat and fatty acids Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids National Academies Press, Washington DC, pp 422–541 141 Jalal F, Nesheim MC, Agus Z, Sanjur D, Habicht JP (1998) Serum retinol concentrations in children are affected by food sources of beta-carotene, fat intake, and anthelmintic drug treatment Am J Clin Nutr 68:623–629 142 Christensen JH, Christensen MS, Dyerberg J, Schmidt EB (1999) Heart rate variability and fatty acid content of blood cell membranes: a dose response study with n-3 fatty acids Am J Clin Nutr 70:331–337 143 Smuts CM, Huang M, Mundy D, Plasse T, Major S, Carlson SE (2003) A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy Obstet Gynecol 101:469–479 144 Reiffel JA, McDonald A (2006) Antiarrhythmic effects of omega-3 fatty acids Am J Cardiol 98:50i–60i 145 Tocher D (2009) Issues surrounding fish as a source of o-3 long chain polyunsaturated fatty acids Lipid Technol 21:13–16 146 Harwood JL (1988) Fatty acid metabolism Annu Rev Plant Physiol Plant Mol Biol 39:101–138 147 Somerville C, Browse J (1991) Plant lipids: metabolism, mutants and membranes Science 252:80–87 148 Ohlrogge JB, Jaworski JG (1997) Regulation of fatty acid synthesis Annu Rev Plant Physiol Plant Mol Biol 48:109–136 149 Ohlrogge J, Browse J (1995) Lipid biosynthesis Plant Cell 7:957–970 150 Sasaki Y, Nagano Y (2004) Plant acetyl-CoA carboxylase: structure, biosynthesis, regulation, and gene manipulation for plant breeding Biosci Biotechnol Biochem 68:1175–1184 151 Ruiz-Lo´pez N, Sayanova O, Napier JA, Haslam RP (2012) Metabolic engineering of the omega-3 long chain polyunsaturated fatty acid biosynthetic pathway into transgenic plants J Exp Bot 63:2397–2410 152 Zou J, Katavic V, Giblin EM, Barton DL, MacKenzie SL, Keller WA, Hu X, Taylor DC (1997) Modification of seed oil content and the acyl composition in the Brassicaceae by expression of a yeast sn-2 acyltransferase gene Plant Cell 9:909–923 153 Yuan L, Knauf VC (1997) Modification of plant components Curr Opin Biotechnol 8:227–233 154 Napier JA (2007) The production of unusual fatty acids in transgenic plants Annu Rev Plant Biol 58:295–319 155 Kinney AJ, Knowlton S (1998) Designer oils: the high oleic acid soybean In: Roller S, Harlander S (eds) Genetic modification in the food industry Blackie Academic and Professional, London, pp 193–213 156 Dehesh K, Jones A, Knutzon DS, Voelker TA (1996) Production of high levels of 8:0 and 10:0 fatty acids in transgenic canola by overexpression of Ch FatB2, a thioesterase cDNA from Cuphea hookeriana Plant J 9:167–172 157 Ursin VM (2003) Modification of plant lipids for human health: development of functional land-based omega-3 fatty acids J Nutr 133:4271–4274 56 Functional Foods: Genetics, Metabolome, and Engineering Phytonutrient Levels 1749 158 Arcadia Biosciences (2008) Arcadia Biosciences and Bioriginal Food and Science Corporation Enter strategic alliance to market high GLA safflower oil http://findarticles.com/p/ articles/mi_m0EIN/is_/ai_n24320185 (February 22, 2008) 159 Nykiforuk CL, Shewmaker C, Harry I et al (2011) High level accumulation of gamma linolenic acid (C18:3D6.9,12 cis) in transgenic safflower (Carthamus tinctorius) seeds Transgenic Res 21:367–381 160 Wakita Y, Otani M, Hamada T, Mori M, Iba K, Shimada T (2001) A tobacco microsomal o-3 fatty acid desaturase gene increases the linolenic acid content in transgenic sweet potato (Ipomoea batatas) Plant Cell Rept 20:244–249 161 Domı´nguez T, Herna´ndez ML, Pennycooke JC, Jime´nez P, Martı´nez-Rivas JM, Sanz C, Stockinger EJ, Sa´nchez-Serrano JJ, Sanmartı´n M (2010) Increasing o-3 desaturase expression in tomato results in altered aroma profile and enhanced resistance to cold stress Plant Physiol 153:655–665 162 Simkin AJ, Gaffe´ J, Alcaraz J-P, Carde J-P, Bramley PM, Fraser PD, Kuntz M (2007) Fibrillin influence on plastid ultrastructure and pigment content in tomato fruit Phytochemistry 68:1545–1556 163 Fineberg HV, Rowe S (1998) Improving public understanding: guidelines for communicating emerging science on nutrition, food safety and health J Natl Cancer Inst 90:194–199 Part VI Phenolics: Classes - Occurrence, Biosynthesis, Structure and Chemistry, Distribution Flavanols: Catechins and Proanthocyanidins 57 Joana Oliveira, Nuno Mateus, and Victor de Freitas Contents Introduction Structural Features 2.1 Flavanol Monomers 2.2 Proanthocyanidins Biosynthesis Occurrence Proanthocyanidin-Protein Interaction Copigmentation Chemical Transformations Conclusion References 1755 1755 1755 1756 1761 1764 1766 1781 1782 1787 1788 Abstract Flavanols are a wide group of polyphenols that include flavan-3-ols (e.g., catechin and proanthocyanidins), flavan-4-ols, and flavan-3,4-diols They arise from plant secondary metabolism through condensation of phenylalanine derived from the shikimate pathway with malonyl-CoA obtained from citrate that is produced by the tricarboxylic acid cycle, leading to the formation of the key precursor in the flavonoids biosynthesis: the naringenin chalcone The exact nature of the molecular species that undergo polymerization and the mechanism of assembly in proanthocyanidins are still unknown From a structural point of view, flavanols J Oliveira • V de Freitas (*) Departamento de Quı´mica, Faculdade de Cieˆncias, Centro de Investigac¸a˜o em Quı´mica, Universidade Porto, Porto, Portugal e-mail: jsoliveira@fc.up.pt; vfreitas@fc.up.pt N Mateus Department of Chemistry and Biochemistry, Chemistry Investigation Centre (CIQ), Universidade Porto, Porto, Portugal K.G Ramawat, J.M Me´rillon (eds.), Natural Products, DOI 10.1007/978-3-642-22144-6_58, # Springer-Verlag Berlin Heidelberg 2013 1753 1754 J Oliveira et al comprise a C15 (C6-C3-C6) general structure composed by a benzopyran moiety (A and C rings) with an additional aromatic ring (B ring) linked to carbon C-2 of C ring Flavanols are present in nature in monomeric, oligomeric, and polymeric forms and differ from each other essentially in the configuration of carbon C-2, the hydroxylation/methoxylation pattern of the rings, the type of linkage between each unit, and the degree of galloylation Flavanols in foods are described to present several beneficial effects such as antioxidant and anticarcinogenic properties and also contribute to the sensory properties of some food products, such as astringency and color Some of these aspects are discussed herein Keywords Biosynthesis • Chemical reactions • Flavan-3,4-diols • Flavan-3-ols • Flavan-4ols • Flavanols • Occurrence • Proanthocyanidins • Structural features Abbreviations 4CL ANR ANS C C3G C4H CGCC CHI CHS DFR DP E3G EC EC3G EGC EEC EGC3G F30 50 H F3H F30 H GC GC3G GCCC GCGCC HCA-CoA HMF HPLC LAR MW PAL 4-Coumarate:CoA ligase Anthocyanidin reductase Anthocyanidin synthase Catechin Catechin-3-O-gallate Cinnamate 4-hidroxylase Catechin-gallocatechin-catechin Chalcone isomerase Chalcone synthase Dihydroxyflavonol 4-reductase Degree of polymerization Epicatechin-3-O-glucoside Epicatechin Epicatechin-3-O-gallate Epigallocatechin Epicatechin-epicatechin-catechin Epigallocatechin-3-O-gallate Flavonoid 30 ,50 -hydroxylase Flavanone 3b-hydroxylase Flavonoid 30 -hydroxylase Gallocatechin Gallocatechin-3-O-gallate Gallocatechin-catechin-catechin Gallocatechin-gallocatechin-catechin Hydroxycinnamic acid-CoA Hydroxymethylfurfural High-performance liquid chromatography Leucoanthocyanidin reductase Molecular weight Phenylalanine ammonia lyase 57 Flavanols: Catechins and Proanthocyanidins PAs PCs PDs PPO PRPs 1755 Proanthocyanidins Procyanidins Prodelphinidins Polyphenol oxidase Proline-rich proteins Introduction Flavanol monomers and proanthocyanidins (syn condensed tannins) are polyphenolic compounds derived from plant secondary metabolism being present in a wide variety of plants and plant-derived foods such as fruits, cereals, seeds, wines, ciders, teas, beers, and cocoa [1–7] Flavanols are involved in the protection against the abiotic (e.g., sunlight) and the biotic stress (e.g., predation, pathogen attack) of plants [8, 9] Proanthocyanidins (PAs) have the capacity to interact and precipitate alkaloids and proteins [10, 11] Their ability to precipitate salivary proteins in the oral cavity is described to be at the origin of the astringency character that is generally associated to tanninrich foods [11–13] Flavanols can also contribute to the color of some food products such as red wines, in one hand through their association with anthocyanins (copigmentation phenomenon) enhancing the color of red wines [14–19] and on the other hand by their chemical reaction with anthocyanins leading to the formation of new colored compounds with different spectroscopic features [20–26] Furthermore, flavanols may form stable complexes with metal ions [27–30] influencing the bioavailability of several minerals [31, 32] Like other polyphenols, flavanols are good reducing agents showing important antioxidant and radicalscavenging properties [33–36] Based on these properties, numerous studies have been published evidencing PAs health benefits over the last years Proanthocyanidins have been shown to prevent low-density lipoproteins [37–40] and lipid peroxidation [41–44] and also to inhibit platelet aggregation [45, 46], which are two major mechanisms described to be at the origin of arteriosclerosis and cardiovascular diseases [47, 48] Several in vitro studies have also suggested a protective role of PAs against several types of cancers [49–51] More recently, PAs have been shown to present some antinutritional effects as they were found to inhibit the three main classes of digestive enzymes: lipases [52], glycosidases [53], and proteases [54, 55] Structural Features 2.1 Flavanol Monomers Flavan-3-ols, flavan-4-ols, and flavan-3,4-diols are different classes of flavonoid compounds comprising a C15 (C6-C3-C6) general structure of a benzopyran moiety (A and C rings) that presents an aromatic ring (B ring) linked to carbon C-2 of 1756 J Oliveira et al Fig 57.1 General structure of the flavanic core 3Ј 4Ј 2Ј B 8a O A 5Ј 1Ј 6Ј C 4a pyranic ring C (Fig 57.1) The difference between each of these classes is in the hydroxylation pattern of the pyran ring On the other hand, in the case of flavan-3-ols, flavan-4-ols, and flavan-3,4-diols, there is a hydroxyl group present at carbon C-3, C-4 or C-3, and C-4, respectively In the case of flavans, there is no hydroxyl group in the pyranic ring However, these latter are more rarely found in nature [56–58] Flavan-4-ols and flavan-3,4-diols are also unlikely to be detected in nature due to their high reactivity as electrophiles in weakly acidic conditions [59, 60] On the other hand, flavan-3-ols are very abundant in nature (Table 57.1), and their structures differ from each other in the stereochemistry of the asymmetric carbons (C-2 and C-3) of the pyranic ring C and in the hydroxylation pattern of rings A and B The most common flavan-3-ols in plant kingdom are hydroxylated at carbons C-5 and C-7 in ring A, differing only in the hydroxylation pattern of ring B and in the stereochemistry of carbon C-3 from ring C [62, 63] (Fig 57.2) Carbon C-2 in the naturally occurring flavan-3-ols is almost exclusively present in the 2R configuration The less common flavan-3-ols presenting a carbon C-2 with a 2S configuration are named with the prefix ent, as in ent-catechin ((À)-catechin) that has a 2S,3R absolute configuration [63, 64] The carbon C-3 can be found in the 3S or 3R configuration For example, in flavan-3-ols with an ortho-dihydroxylated ring B (C-30 ,C-40 ), two situations may be observed: carbons C-2 and C-3 present a 2R,3S absolute configuration (trans conformation) like in (+)-catechin or present a 2R,3R configuration (cis conformation) as in (À)-epicatechin (Fig 57.2) Flavan-3-ols with a 3R absolute configuration in carbon C-3 present the prefix epi Furthermore, ring B monohydroxylated and trihydroxylated give rise to (+)-afzelechin or (À)-epiafzelechin, (+)-gallocatechin or (À)-epigallocatechin, respectively (Fig 57.2) Flavan-3-ols can also be esterified with gallic acid or glucosylated in the hydroxyl group of carbon C-3 of the pyranic ring C [65, 66], although the glucosylated forms are scarce in the plant kingdom [63, 67, 68] (Fig 57.3) 2.2 Proanthocyanidins Proanthocyanidins are oligomeric or polymeric chains of flavan-3-ols that are present in nature in a great diversity of structures This is due to structural features of the monomeric units and also to the type of interflavanic bond, the degree of polymerization, and esterification with gallic acid [69, 70] 19.6 10.6 70.3 28.1 30.2 6.5 58.0 17.7 585.5 27.2 67.7 42.2 40.0 22.1 ND 55.5 51.4 67 80 664.0 3.4 1.7 13.1 6.5 1.2 1.9 12.5 5.5 50 0.6 20.3 5.2 8.5 3.3 3.5 9.8 8.2 Ỉ Ỉ Ỉ Ỉ Ỉ Ỉ Ỉ Ỉ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ 14.5 9.9 62.9 23.9 25.4 4.6 33.8 10.9 734.3 ND 74.6 37.9 37.7 5.4 ND 38.5 35.3 ND 50 69 400.3 1.4 14.7 3.5 1.2 11.9 3.7 69.3 129.0 122.4 233.5 75.8 37.6 ND 13.1 57.3 22.0 2440.4 ND Ỉ 21.9 322.4 Ỉ 4.9 122.5 Ỉ 8.4 80.3 Ỉ 0.8 20.0 ND Ỉ 68.2 Ỉ 7.2 32.8 ND 110 Ỉ Ỉ 303 Ỉ 31.3 1100.1 Ỉ Ỉ Ỉ Ỉ Ỉ Æ Æ Æ Æ Æ b Type: PP propelargonidins, PC procyanidins; PD prodelphinidins; A-polymers with A-type linkage Apple Red Delicious; Apple juice Red Delicious peeled a 1.2 0.3 3.4 1.2 0.4 0.9 5.1 1.4 7.7 3.9 1.2 1.7 1.2 3.5 0.8 2.6 4.5 47.3 28 49.1 13.4 2.6 179.8 147.8 418.8 145.0 125.8 Ỉ 11.3 31.9 Ỉ 24.4 215.9 Ỉ 7.7 67.3 Ỉ 271 3965.4 74.2 Ỉ 102.5 500.7 Ỉ 37.1 237.3 Ỉ 28.1 184.0 Ỉ 9.3 67.3 13.2 Ỉ 8.8 246.0 Ỉ 9.2 192.0 23 Ỉ 313 Ỉ 524 Ỉ 86.3 3532.3 Ỉ Ỉ Ỉ Ỉ Ỉ Total Ỉ Ỉ Ỉ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ Æ 50.8 33 75.3 24.9 6.8 7.8 50.7 20.9 402.5 152 52 48.2 14.7 5.2 0.3 28.8 105.8 PC PC PD A PC PP PC PC PC PC A PC PC PC PC PC PD PC PD PP PC PC A PC PC PC PC PD PC PD PC PD PC Typea Degree of polymerization Product (mg/100 g fresh weight or mg/L for drinks) Blueberry 4.0 Ỉ 1.5 7.2 Ỉ 1.8 5.4 Ỉ Black currant 0.9 Ỉ 0.2 2.9 Ỉ 0.4 3.0 Ỉ Cranberry 7.3 Ỉ 1.5 25.9 Ỉ 6.1 18.9 Ỉ Strawberry 4.2 Æ 0.7 6.5 Æ 1.3 6.5 Æ 9.6 Æ 0.9 13.8 Ỉ 0.6 9.3 Ỉ Appleb Ỉ Æ Æ Apple juiceb Pear 2.7 Æ 1.5 2.8 Ỉ 1.3 2.3 Ỉ Prune 11.4 Ỉ 3.4 31.5 Æ 7.4 23.9 Æ Peach 4.7 Æ 1.4 7.0 Æ 2.2 5.0 Ỉ Sorghum 27.8 Ỉ 1.2 78.2 Ỉ 3.4 99.2 Ỉ Barley 11.0 Ỉ 0.3 21.4 Ỉ 1.1 14.6 Æ Hazelnut 9.8 Æ 1.6 12.5 Æ 3.8 13.6 Æ Pistachio 10.9 Ỉ 4.3 13.3 Ỉ 1.8 10.5 Ỉ Almond 7.8 Ỉ 0.9 9.5 Ỉ 1.6 8.8 Ỉ Walnut 6.9 Æ 3.4 5.6 Æ 0.9 7.2 Æ Peanut (butter) 2.0 Æ 0.9 3.0 Æ 0.7 8.1 Æ Dark chocolate 31.4 Æ 0.2 31.2 Æ 0.9 21.1 Æ Milk chocolate 26.9 Æ 26.2 Æ 2.5 19.3 Æ Bear Æ 11 Ỉ Ỉ Red wine 20 Ỉ 40 Ỉ 27 Ỉ Grape (juice) 18 Ỉ 34 Ỉ 19 Ỉ Grape (dry seed) 660.3 Æ 8.3 417.3 Æ 4.8 290.2 Æ >10 Table 57.1 Distribution and degree of polymerization of the proanthocyanidins in food products [61] 7–10 Flavanols: Catechins and Proanthocyanidins 4–6 57 1757 .. .Natural Products Kishan Gopal Ramawat Jean-Michel Me´rillon Editors Natural Products Phytochemistry, Botany and Metabolism of Alkaloids, Phenolics and Terpenes With 15 69 Figures and 307... Analysis of Ergot Alkaloids 11 33 Colin Crews 36 Analysis of Alkaloids by Capillary Electrophoresis 11 53 Roberto Gotti Part IV Alkaloids: Pharmacology 12 01 37 Pharmacology... Chakraborty and Amita Pal 11 1 Methods for Extraction and Analysis of Carotenoids 3367 Siti Machmudah and Motonobu Goto Part XIII 3 311 Terpenes: Pharmacology and Bioavailability