Chemistry and Synthetic Overview of Flavonoids

  • Ajay Sharma
  • Hardeep Singh Tuli
  • Anil K. Sharma


Flavonoids are widely distributed secondary metabolites in plants that are known to be present in different vegetables and fruits. The flavonoid groups include various subclasses of compounds such as flavanones, flavones, dihydroflavonols, flavonols, flavan-3-ols, anthocyanidins, isoflavones, proanthocyanidins, and chalcones with a C6-C3-C6 structure. These compounds are considered to be imperative structural motifs owing to their distinctive way of physiological action and biochemical effects in humans as well as in plants. Keeping in view of their immense importance and physiological roles, the summation of the structural features is quintessential for their therapeutic applications. Furthermore, the structure-activity relationship together with their chemical and biochemical synthetic preview could help the scientific community to explore and design novel drugs. Therefore, structural features of flavonoids may prompt a great deal of attention in the field of organic synthesis and biology to study innovative methods of synthesis and therapeutic applications.


Flavonoids Structural features Structure-activity relationship (SAR) 



The authors would like to acknowledge the assistance of Career Point University, in Tikker – kharwarian, Hamirpur, Himachal Pradesh, and Maharishi Markandeshwar (deemed to be university) in Mullana, Ambala, Haryana, for providing the required facilities to complete this study.

Conflict of Interest

There exists no conflict of interest among authors regarding the publication of this book chapter.


  1. Andersen QM, Markham KR (2006) Flavonoids: chemistry, biochemistry and applications. CRC Press, Taylor & Francis Group, Boca RatonGoogle Scholar
  2. Batra P, Sharma AK (2013) Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 3(6):439CrossRefGoogle Scholar
  3. Bhagwat S, Haytowits DB, Holden JM (2013) Usda database for the flavonoid content of selected foods. Release 3.1. Nutrient Data Laboratory, Beltsville Human Nutrition Research Center Agricultural Research Service U.S. Department of Agriculture, Beltsville, pp 1–155Google Scholar
  4. Bianco A, Cavarischia C, Guiso M et al (2003) A new synthesis of flavonoids via Heck reaction. Tetrahedron Lett 44:9107–9109CrossRefGoogle Scholar
  5. Bianco A, Cavarischia C, Guiso M (2004) The Heck coupling reaction using aryl vinyl ketones: synthesis of flavonoids. Eur J Org Chem 2004:2894–2898. CrossRefGoogle Scholar
  6. Bone K, Mills S (2013) Chapter 2 – principles of herbal pharmacology principles and practice of phytotherapy. In: Modern herbal medicine, 2nd edn. Elsevier, Amsterdam, pp 17–82. CrossRefGoogle Scholar
  7. Cazarolli LH, Kappel VD, Zanatta AP et al (2013) Natural and synthetic chalcones: tools for the study of targets of action – insulin secretagogue or insulin mimetic? In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 39. Elsevier, Amsterdam, pp 47–89Google Scholar
  8. Chang H, Mi M, Ling W et al (2010) Structurally related anticancer activity Of flavonoids: involvement of reactive oxygen species generation. J Food Biochem 34:1–14. CrossRefGoogle Scholar
  9. Chen L, Teng H, Xie Z et al (2016) Modifications of dietary flavonoids towards improved bioactivity: an update on structure–activity relationship. Crit Rev Food Sci Nutr 58:513–527. CrossRefGoogle Scholar
  10. Correia-da-Silva M, Sousa E, Pinto MMM (2013) Emerging sulfated flavonoids and other polyphenols as drugs: nature as an inspiration. Med Res Rev 34(2):1–57. CrossRefGoogle Scholar
  11. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352. CrossRefPubMedPubMedCentralGoogle Scholar
  12. de la Rosa LA, Alvarez-Parrilla E, Gonzalez-Aguilar GA (2010) Fruit and vegetable phytochemicals: chemistry, nutritional value, and stability, 1st edn. Wiley, AmesGoogle Scholar
  13. Erdman JW Jr, Balentine D, Arab L et al (2007) Flavonoids and heart health: proceedings of the ILSI North America flavonoids workshop, May 31–June 1, 2005, Washington, DC. J Nutr 137:718S–737SCrossRefGoogle Scholar
  14. Erlejman AG, Verstraeten SV, Fraga CG et al (2004) The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects. Free Radic Res 38:1311–1320CrossRefGoogle Scholar
  15. Ferreyra MLF, Rius SP, Casati P (2012) Flavonoids: biosynthesis, biological functions, and biotechnological applications Front. Plant Sci 3:222. CrossRefGoogle Scholar
  16. Gomes MN, Muratov EN, Pereira M et al (2017) Chalcone derivatives: promising starting points for drug design. Molecules 22(8):1210. CrossRefGoogle Scholar
  17. Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 13:572–584CrossRefGoogle Scholar
  18. Hrazdina G (1992) Biosynthesis of flavonoids. In: Hemingway RW, Laks PE (eds) Plant polyphenols. Basic life sciences, vol 59. Springer, BostonGoogle Scholar
  19. Kakati D, Sarma JC (2011) Microwave assisted solvent free synthesis of 1,3-diphenylpropenones. Chem Cent J 5:8. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kashyap D, Sharma A, Tuli HS et al (2017) Kaempferol – a dietary anticancer molecule with multiple mechanisms of action: recent trends and advancements. J Funct Foods 30:203–219CrossRefGoogle Scholar
  21. Kashyap D, Sharma A, Sak K et al (2018) Fisetin: a bioactive phytochemical with potential for cancer prevention and pharmacotherapy. Life Sci 194:75–87CrossRefGoogle Scholar
  22. Khare R, Sharma J, Sharma A (2016) Russ J Gen Chem 86:702. CrossRefGoogle Scholar
  23. Kitagawa S (2006) Inhibitory effects of polyphenols on P-glycoprotein-mediated transport. Biol Pharm Bull 29(1):1–6CrossRefGoogle Scholar
  24. Kozłowska A, Szostak-Węgierek D (2014) Flavonoids – food sources and health benefits. Rocz Panstw Zakl Hig 65(2):79–85Google Scholar
  25. Kshatriya R, Jejurkar VP, Saha S (2018) In memory of Prof. Venkataraman: recent advances in the synthetic methodologies of flavones. Tetrahedron 74:811–833CrossRefGoogle Scholar
  26. Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013:162750, 16 pages. CrossRefGoogle Scholar
  27. Kumar S, Lamba MS, Makrandi JK (2008) An efficient green procedure for the synthesis of chalcones using C-200 as solid support under grinding conditions. Green Chem Lett Rev 1(2):123–125. CrossRefGoogle Scholar
  28. Li J (ed) (2005) Name reactions in heterocyclic Chemistry. Wiley, Hoboken, pp 262–265Google Scholar
  29. Li JJ (2009a) Algar— Flynn— Oyamada reaction. In: Li JJ (ed) Name reactions. Springer, Berlin/Heidelberg. CrossRefGoogle Scholar
  30. Li JJ (2009b) Allan–Robinson reaction. In: Li JJ (ed) Name reactions. Springer, Berlin/Heidelberg. CrossRefGoogle Scholar
  31. Li JJ (2009c) Baker–Venkataraman rearrangement. In: Li JJ (ed) Name reactions. Springer, Berlin/Heidelberg. CrossRefGoogle Scholar
  32. Lopez-Lazaro M (2002) Flavonoids as anticancer agents: structure-activity relationship study. Curr Med Chem Anticancer Agents 2(6):691–714CrossRefGoogle Scholar
  33. Miranda CL, Maier CS, Stevens JF (2012) Flavonoids. In: eLS.
  34. Morreel K, Goeminne G, Storme V et al (2006) Genetical metabolomics of flavonoid biosynthesis in Populus: a case study. Plant J 47:224–237. CrossRefGoogle Scholar
  35. Nambi RA, Viswanathan S, Thirugnanasambantham P et al (1996) Anti-inflammatory activity of flavone and its Hydroxy derivatives-a structure activity study. Indian J Pharm Sci 58(1):18Google Scholar
  36. Prochazkova D, Bousova I, Wilhelmova N (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia 82(4):513–523CrossRefGoogle Scholar
  37. Qian H, Wang Y, Liu D (2013) Ultrasound-accelerated synthesis of substituted 2′-hydroxychalcones by reusable ionic liquids. Ind Eng Chem Res 52(37):13272–13275. CrossRefGoogle Scholar
  38. Ravishankar D, Rajora AK, Greco F, Osborn HM (2013) Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell Biol 45(12):2821–2831CrossRefGoogle Scholar
  39. Selepe MA, Heerden FRV (2013) Application of the Suzuki-Miyaura reaction in the synthesis of flavonoids. Molecules 18:4739–4765. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Sharma A, Khare R, Kumar V et al (2014) 1-(Substituted)-4, 4, 6-trimethyl-3, 4-dihydropyrimidine-2(1H)-thione: green synthesis, antibacterial activity and DNA photocleavage activity. Int J Pharm Pharm Sci 6(3):171–175Google Scholar
  41. Sharma A, Kumar V, Khare R et al (2015) Synthesis, docking study, and DNA photocleavage activity of some pyrimidinylhydrazones and 3-(quinolin-3-yl)-5, 7-dimethyl-1, 2, 4-triazolo [4, 3-a] pyrimidine derivatives. Med Chem Res 24(5):1830–1841CrossRefGoogle Scholar
  42. Sharma A, Sharma P, Singh HT et al (2018a) Phytochemical and pharmacological properties of flavonols. In: eLS. Wiley.
  43. Sharma A, Kashyap D, Sak K et al (2018b) Therapeutic charm of quercetin and its derivatives: a review of research and patents. Pharm Pat Anal 7(1):15–32. CrossRefGoogle Scholar
  44. Stoyanov EV, Champavier Y, Simon A et al (2002) Efficient liquid-phase synthesis of 2′-hydroxychalcones. Bioorg Med Chem Lett 12(19):2685–2687CrossRefGoogle Scholar
  45. Teles YCF, Souza MSR, Vanderlei de Souza MF (2018) Sulphated flavonoids: biosynthesis, structures, and biological activities. Molecules 23:480. CrossRefPubMedPubMedCentralGoogle Scholar
  46. Wagner H, Farkas L (1975) Synthesis of flavonoids. In: Harborne JB, Mabry TJ, Mabry H (eds) The flavonoids. Springer, BostonGoogle Scholar
  47. Wang Z (2010a) Algar-Flynn-Oyamada (AFO) reaction. In: Wang Z (ed) Comprehensive organic name reactions and reagents. doi:
  48. Wang Z (2010b) Allan-Robinson condensation. In: Wang Z (ed) Comprehensive organic name reactions and reagents.
  49. Wang Z (2010c) Baker-Venkataraman rearrangement. In: Wang Z (ed) Comprehensive organic name reactions and reagents.
  50. Wang Z (2010d) Mentzer Pyrone synthesis. In: Wang Z (ed) Comprehensive organic name reactions and reagents.
  51. Wang X, Morris ME (2014) Diet/nutrient interactions with drug transporters. In: You G, Morris ME (eds) Drug transporters, 2nd edn. John, Hoboken, pp 409–427. CrossRefGoogle Scholar
  52. Wen L, Jiang Y, Yang J et al (2017) Structure, bioactivity, and synthesis of methylated flavonoids. Ann NY Acad Sci 1398:120–129. CrossRefGoogle Scholar
  53. Zandena JJV, Wortelboerb HM, Bijlsmab S et al (2005) Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2. Biochem Pharmacol 69:699–708CrossRefGoogle Scholar
  54. Zhuang C, Zhang W, Sheng C et al (2017) Chalcone: a privileged structure in medicinal chemistry. Chem Rev 117(12):7762–7810. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Ajay Sharma
    • 1
  • Hardeep Singh Tuli
    • 2
  • Anil K. Sharma
    • 2
  1. 1.Department of ChemistryCareer Point UniversityHamirpurIndia
  2. 2.Department of BiotechnologyMaharishi Markandeshwar (Deemed to be University)Mullana-AmbalaIndia

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