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A Short Review on Synthetic Methodologies of Flavonoids


Affiliations
1 Department of Chemistry, Lahore Garrison University, Lahore, Pakistan
2 Department of Chemistry, School of Science, University of Management and Technology, Lahore, Pakistan
     

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Flavonoids are the pigments present in plants which mostly found in terrestrial plants. Flavonoids are indeed a naturally present group of polyphenolic compounds present in plants. They were driven by the term "flavus," which means "yellow." It is a 15-carbon skeleton compound. They have fused aromatic ring and benzopyran heterocyclic ring having oxygen atom in it along with phenyl substituent. They are synthesized from Phenylalanine. In cereals and Herbs, they are mainly found. Flavonoids are compounds that are biologically active. They provide color and protection from ultraviolet rays. They have many classes based upon oxidative status, number, and types of substituents present. Flavonoids exist naturally in the form of polymers, most commonly in dimers form. They occur primarily in β-glycosides form except for Catechins. They can help in the inhibition of enzymes and stimulate some hormones along with some neurotransmitters. They also show the properties of scavenging free radicals. They can inhibit or kill many bacterial strains, viral enzymes, and pathogenic protozoans. There are various techniques and methods for the synthesis of natural products artificially. In the present study, we have attempted to cover different synthetic methods for flavonoid synthesis to find its best way to synthesize. It was concluded that Baker & Venkatraman synthesis and Claisen-Schmidt condensation are well-known methods used to synthesize flavonoids.

Keywords

Flavonoids, Polyphenols, Phenylalanine, Baker & Venkatraman, Claisen-Schmidt
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  • Singh D, Sharma S, Rani R, Mishra S, Sharma RJAJoRiC. A new flavonoid and other two flavonoids isolated from different plant parts of selected Cassia species. 2011; 4(5):818-21.

  • Khanahmadi M, Shahrezaei F, Alizadeh AJAJoRiC. Isolation and structural elucidation of two flavonoids from Ferulago angulata (Schlecht) Boiss. 2011; 4(11):1667-70.

  • Tiwari PJAJPA. Phenolics and flavonoids and antioxidant potential of balarishta prepared by traditional and modern methods. 2014; 4:5-10.

  • Tiwari P, Patel RKJAJoPA. Estimation of total phenolics and flavonoids and antioxidant potential of Ashwagandharishta prepared by traditional and modern methods. 2013; 3(4):147-52.

  • Castellano G, González-Santander JL, Lara A, Torrens F. Classification of flavonoid compounds by using entropy of information theory. Phytochemistry. 2013; 93:182-91.

  • Iwashina T. The structure and distribution of the flavonoids in plants. J Plant Res. 2000; 113(3):287.

  • Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem. 2017; 142:213-28.

  • Ashfaq MH, Siddique A, Shahid SJAJoPR. Antioxidant Activity of Cinnamon zeylanicum:(A Review). 2021; 11(2):106-16.

  • Šmejkal K, Malaník M, Zhaparkulova K, Sakipova Z, Ibragimova L, Ibadullaeva G, et al. Kazakh Ziziphora species as sources of bioactive substances. Molecules (Basel, Switzerland). 2016; 21(7):826.

  • Kumar S, Pandey AK. Chemistry and biological activities of flavonoids: an overview. The scientific world journal. 2013; 2013.

  • Amic D, Davidovic-Amic D, Beslo D, Rastija V, Lucic B, Trinajstic N. SAR and QSAR of the antioxidant activity of flavonoids. Curr Med Chem. 2007; 14(7):827-45.

  • Middleton E. Effect of plant flavonoids on immune and inflammatory cell function. Flavonoids in the living system: Springer; 1998. p. 175-82.

  • Madunić J, Madunić IV, Gajski G, Popić J, Garaj-Vrhovac V. Apigenin: A dietary flavonoid with diverse anticancer properties. Cancer Lett. 2018; 413:11-22.

  • Martínez G, Mijares MR, De Sanctis JB. Effects of Flavonoids and Its Derivatives on Immune Cell Responses. Molecules (Basel, Switzerland). 2019; 13(2):84-104.

  • Nichenametla SN, Taruscio TG, Barney DL, Exon JH. A review of the effects and mechanisms of polyphenolics in cancer. Crit Rev Food Sci Nutr. 2006; 46(2):161-83.

  • Irshad M, Ali Q, Abbasi MA, Iram F, Saadia M, Ishfaq MHJPJoPS. Synthesis, spectral characterization and antimicrobial studies of novel series of allylidene based multifaceted chalcones analogues. 2020; 33(3).

  • Mallavadhani UV, Mahapatra A. A new aurone and two rare metabolites from the leaves of Diospyros melanoxylon. Nat Prod Res. 2005; 19(1):91-7.

  • Rao KP, Kumari KS, Mohan SJI. Synthesis, Characterization and Antimicrobial activity of Some Flavones. 2013; 13(13.85):2.

  • Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflammation & Allergy-Drug Targets (Formerly Current Drug Targets-Inflammation & Allergy). 2010; 9(4):263-85.

  • Nile SH, Keum YS, Nile AS, Jalde SS, Patel RV. Antioxidant, anti‐inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives. J Biochem Mol Toxicol. 2018; 32(1):e22002.

  • Singh D, Sharma SK, Shekhawat M, Yadav K, Sharma R, Bansal A, et al. Screening of Some Glycosidic Flavonoids and their Anti Microbial Activity of Cassia Pumila Lamk. 2012; 5(2):305-11.

  • Kumar MS, Balachandran S, Chaudhury SJAJPR. Influence of incubation temperatures on total phenolic, flavonoids content and free radical scavenging activity of callus from Heliotropium indicum L. 2012; 2(4):148-52.

  • Panche A, Diwan A, Chandra S. Flavonoids: an overview. Journal of nutritional science. 2016; 5.

  • Mays JR, Hill SA, Moyers JT, Blagg BS. The synthesis and evaluation of flavone and isoflavone chimeras of novobiocin and derrubone. Biorg Med Chem. 2010; 18(1):249-66.

  • Tandon V, Das B. Genistein: is the multifarious botanical a natural anthelmintic too? J Parasit Dis. 2018; 42(2):151-61.

  • Chakrawarti L, Agrawal R, Dang S, Gupta S, Gabrani R. Therapeutic effects of EGCG: a patent review. Expert Opin Ther Pat. 2016; 26(8):907-16.

  • Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrients. 2010; 2(12):1231-46.

  • Hua S, Zhang Y, Liu J, Dong L, Huang J, Lin D, et al. Ethnomedicine, phytochemistry and pharmacology of Smilax glabra: An important traditional Chinese medicine. The American Journal of Chinese Medicine. 2018; 46(02):261-97.

  • D Archivio M, Filesi C, Di Benedetto R, Gargiulo R, Giovannini C, Masella R. Polyphenols, dietary sources and bioavailability. Annali-Istituto Superiore di Sanita. 2007; 43(4):348.

  • Stalikas CD. Extraction, separation, and detection methods for phenolic acids and flavonoids. J Sep Sci. 2007; 30(18):3268-95.

  • Ramasubramaniaraja RJAJoPA. Pharmacognostical phytochemical including GC-MS investigation of ethanolic leaf extracts of Abutilon indicum (Linn). 2011; 1(4):88-92.

  • K Sahu N, S Balbhadra S, Choudhary J, V Kohli D. Exploring pharmacological significance of chalcone scaffold: a review. Curr Med Chem. 2012; 19(2):209-25.

  • Yang N, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, et al. Glycyrrhiza uralensis flavonoids present in anti‐asthma formula, ASHMITM, inhibit memory Th2 responses in vitro and in vivo. Phytother Res. 2013; 27(9):1381-91.

  • Rithiga SB, Shanmugasundaram SJAJoRiPS. Virtual Screening of Pentahydroxyflavone–A Potent COVID-19 Major Protease Inhibitor. 2021; 11(1):7-14.

  • Zheng S-Y, Shen Z-W. Total synthesis of hirtellanine A. Tetrahedron Lett. 2010; 51(21):2883-7.

  • Eddarir S, Cotelle N, Bakkour Y, Rolando C. An efficient synthesis of chalcones based on the Suzuki reaction. Tetrahedron Lett. 2003; 44(28):5359-63.

  • Selepe MA, Drewes SE, van Heerden FR. Total synthesis of the pyranoisoflavone kraussianone 1 and related isoflavones. J Nat Prod. 2010; 73(10):1680-5.

  • Ito F, Iwasaki M, Watanabe T, Ishikawa T, Higuchi Y. The first total synthesis of kwakhurin, a characteristic component of a rejuvenating plant, “kwao keur”: toward an efficient synthetic route to phytoestrogenic isoflavones. Org Biomol Chem. 2005; 3(4):674-81.

  • Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z. Chalcone: a privileged structure in medicinal chemistry. Chemical reviews. 2017; 117(12):7762-810.

  • Haddach M, McCarthy JR. A new method for the synthesis of ketones: The palladium-catalyzed cross-coupling of acid chlorides with arylboronic acids. Tetrahedron Lett. 1999; 40(16):3109-12.

  • Rullah K, Mohd Aluwi MFF, Yamin BM, Juan JC, Wai LK. Palladium‐Catalysed Cross‐Coupling Reactions for the Synthesis of Chalcones. Asian Journal of Organic Chemistry. 2019; 8(8):1174-93.

  • Al-Masum M, Ng E, Wai MC. Palladium-catalyzed direct cross-coupling of potassium styryltrifluoroborates and benzoyl chlorides—A one step method for chalcone synthesis. Tetrahedron Letters. 2011; 52(9):1008-10.

  • Blangetti M, Rosso H, Prandi C, Deagostino A, Venturello P. Suzuki-Miyaura cross-coupling in acylation reactions, scope and recent developments. Molecules (Basel, Switzerland). 2013; 18(1):1188-213.

  • Ayogu JI, Onoabedje EA. Recent advances in transition metal-catalysed cross-coupling of (hetero) aryl halides and analogues under ligand-free conditions. Catalysis Science & Technology. 2019; 9(19):5233-55.

  • Malik I, Hussain M, Hung NT, Villinger A, Langer P. Synthesis of 7, 8-diarylflavones by site-selective Suzuki-Miyaura reactions. Synlett. 2010; 2010(15):2244-6.

  • Selepe MA, Van Heerden FR. Application of the Suzuki-Miyaura reaction in the synthesis of flavonoids. Molecules (Basel, Switzerland). 2013; 18(4):4739-65.

  • Kraus GA, Gupta V. Divergent approach to flavones and aurones via dihaloacrylic acids. Unexpected dependence on the halogen atom. Org Lett. 2010; 12(22):5278-80.

  • Dawood KM. Microwave-assisted Suzuki–Miyaura and Heck–Mizoroki cross-coupling reactions of aryl chlorides and bromides in water using stable benzothiazole-based palladium (II) precatalysts. Tetrahedron. 2007; 63(39):9642-51.

  • Eisnor CR, Gossage RA, Yadav PN. Oxazoline Chemistry. Part 11: Syntheses of natural and synthetic isoflavones, stilbenes and related species via C–C bond formation promoted by a Pd–oxazoline complex. Tetrahedron. 2006; 62(14):3395-401.

  • Dong T, He J, Li Z-H, Zhang C-P. Catalyst-and additive-free trifluoromethylselenolation with [Me4N][SeCF3]. ACS Sustainable Chemistry & Engineering. 2018; 6(1):1327-35.

  • Ramaite ID, Maluleke MD, Mnyakeni-Moleele SS. Synthesis and Evaluation of Isoflavones as Potential Anti-inflammatory Inhibitors. Arabian Journal for Science and Engineering. 2017; 42(10):4263-71.

  • Lee JI. An Efficient and Versatile Synthesis of Isoflavones from 2-Methoxybenzoic Acids. Bull Korean Chem Soc. 2016; 37(7):1132-5.

  • Boland GM, Donnelly DM, Finet J-P, Rea MD. Synthesis of neoflavones by Suzuki arylation of 4-substituted coumarins. J Chem Soc, Perkin Trans 1. 1996(21):2591-7.

  • Khaddour Z, Akrawi OA, Suleiman AS, Patonay T, Villinger A, Langer P. Regioselective Suzuki–Miyaura cross-coupling reactions of the bis (triflate) of 4, 7-dihydroxycoumarin. Tetrahedron Lett. 2014; 55(32):4421-3.

  • Moskvina V, Khilya V. Recent Progress in the Synthesis of 4-Arylcoumarins. Chem Nat Compd. 2019; 55(3):401-27.

  • Jung J-W, Kim N-J, Yun H, Han YT. Recent advances in synthesis of 4-arylcoumarins. Molecules (Basel, Switzerland). 2018; 23(10):2417.

  • Silva VL, Soengas RG, Silva A. Ionic Liquids and Ohmic Heating in Combination for Pd-Catalyzed Cross-Coupling Reactions: Sustainable Synthesis of Flavonoids. Molecules (Basel, Switzerland). 2020; 25(7):1564.

  • Santos CM, Silva AM. An overview of 2‐styrylchromones: natural occurrence, synthesis, reactivity and biological properties. European Journal of Organic Chemistry. 2017; 2017(22):3115-33.

  • Wang X, Liu J, Zhang Y. An Efficient One-Pot Synthesis and Anticancer Activity of 4'-Substituted Flavonoids. Russ J Gen Chem. 2018; 88(5):1036-41.

  • Shaikh RKY, Nazeruddin G. Synthesis of flavone skeleton by different methods. Oriental Journal of Chemistry. 2014; 29(4):1475-87.

  • Venkatachalam H, Nayak Y, Jayashree B. Evaluation of the antioxidant activity of novel synthetic chalcones and flavonols. International Journal of Chemical Engineering and Applications. 2012; 3(3):216.

  • Nhu D, Hawkins BC, Burns CJ. Phase Transfer Catalysis Extends The Scope of The Algar–Flynn–Oyamada Synthesis of 3-Hydroxyflavones. Aust J Chem. 2015; 68(7):1102-7.

  • Shen X, Zhou Q, Xiong W, Pu W, Zhang W, Zhang G, et al. Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication. Tetrahedron. 2017; 73(32):4822-9.

  • Li JJ. Name reactions: a collection of detailed reaction mechanisms: Springer Science & Business Media; 2013.

  • Allan J, Robinson R. CCXC.—An accessible derivative of chromonol. Journal of the Chemical Society, Transactions. 1924; 125:2192-5.

  • Delaude L, Grandjean J, Noels AF. The step-by-step Robinson annulation of chalcone and ethyl acetoacetate. An advanced undergraduate project in organic synthesis and structural analysis. Journal of chemical education. 2006; 83(8):1225.

  • Bansal M, Kaur K, Tomar J, Kaur L. Synthesis of Flavones. Biomedical Journal of Scientific & Technical Research. 2017; 1(6):1752-5.

  • Cushman M, Nagarathnam D. A method for the facile synthesis of ring-A hydroxylated flavones. Tetrahedron Lett. 1990; 31(45):6497-500.

  • Bennardi DO, Romanelli GP, Jios JL, Autino JC, Baronetti GT, Thomas HJ. Synthesis of substituted flavones and chromones using a Wells-Dawson heteropolyacid as catalyst. ARKIVOC. 2008; 2008.

  • Farooq S, Ngaini Z. Recent Synthetic Methodologies for Chalcone Synthesis (2013-2018). Current Organocatalysis. 2019; 6(3):184-92.

  • Ananthnag GS, Adhikari A, Balakrishna MS. Iron-catalyzed aerobic oxidative aromatization of 1, 3, 5-trisubstituted pyrazolines. Catalysis Communications. 2014; 43:240-3.

  • Zhang Z, Wang Y, Wang M, Lu J, Zhang C, Li L, et al. The cascade synthesis of α, β-unsaturated ketones via oxidative C–C coupling of ketones and primary alcohols over a ceria catalyst. Catalysis Science & Technology. 2016; 6(6):1693-700.

  • Farooq S, Ngaini Z, Mortadza NA. Microwave‐assisted Synthesis and Molecular Docking Study of Heteroaromatic Chalcone Derivatives as Potential Antibacterial Agents. Bulletin of the Korean Chemical Society. 2020; 41(9):918-24.

  • Drahl C. In names, history and legacy. CHEMICAL & ENGINEERING NEWS. 2010; 88(20):31-3.

  • Mc Cartney D, Guiry PJ. The asymmetric Heck and related reactions. Chemical Society Reviews. 2011; 40(10):5122-50.

  • Heck RF, Nolley Jr J. Palladium-catalyzed vinylic hydrogen substitution reactions with aryl, benzyl, and styryl halides. The Journal of organic chemistry. 1972; 37(14):2320-2.

  • Hermange P, Gøgsig TM, Lindhardt AT, Taaning RH, Skrydstrup T. Carbonylative Heck reactions using CO generated ex situ in a two-chamber system. Organic letters. 2011; 13(9):2444-7.

  • Hoffmann RW. Wittig and his accomplishments: still relevant beyond his 100th birthday. Angewandte Chemie International Edition. 2001; 40(8):1411-6.

  • Bestmann HJ, Arnason B. Reaktionen mit Phosphin‐alkylenen, II. C‐Acylierung von Phosphin‐alkylenen. Ein neuer Weg zur Synthese von Ketonen. Chemische Berichte. 1962; 95(6):1513-27.

  • Das J, Ghosh S. A new synthesis of flavones and pyranoflavone by intramolecular photochemical Wittig reaction in water. Tetrahedron letters. 2011; 52(52):7189-94.

  • Kumar A, Sharma S, Tripathi VD, Srivastava S. Synthesis of chalcones and flavanones using Julia–Kocienski olefination. Tetrahedron. 2010; 66(48):9445-9.

  • Nielsen M, Jacobsen CB, Holub N, Paixao MW, Jørgensen KA. Asymmetric organocatalysis with sulfones. Angewandte Chemie International Edition. 2010; 49(15):2668-79.

  • Zhang N, Yang D, Wei W, Yuan L, Nie F, Tian L, et al. Silver-Catalyzed Double-Decarboxylative Cross-Coupling of α-Keto Acids with Cinnamic Acids in Water: A Strategy for the Preparation of Chalcones. The Journal of Organic Chemistry. 2015; 80(6):3258-63.

  • Zhou J, Wu G, Zhang M, Jie X, Su W. Pd‐Catalyzed Cross‐Coupling of Aryl Carboxylic Acids with Propiophenones through a Combination of Decarboxylation and Dehydrogenation. Chemistry–A European Journal. 2012; 18(26):8032-6.

  • Shotter R, Johnston K, Jones J. Reactions of unsaturated acid halides—IV: Competitive friedel-crafts acylations and alkylations of monohalogenobenzenes by the bifunctional cinnamoyl chloride. Tetrahedron. 1978; 34(6):741-6.

  • Jaafar NS, Hamad MN, Abbas IS, Jaafar IS. Qualitative phytochemical comparison between flavonoids and phenolic acids contents of leaves and fruits of Melia azedarach (family: Meliaceae) cultivated in Iraq by HPLC and HPTLC. Int J Pharm Pharm Sci. 2016; 8(10):242-50.

  • Maiti G, Karmakar R, Bhattacharya RN, Kayal U. A novel one pot route to flavones under dual catalysis, an organo-and a Lewis acid catalyst. Tetrahedron letters. 2011; 52(43):5610-2.

  • Sabater S, Mata JA, Peris E. Synthesis of Heterodimetallic Iridium–Palladium Complexes Containing Two Axes of Chirality: Study of Sequential Catalytic Properties. European Journal of Inorganic Chemistry. 2013; 2013(27):4764-9.

  • Khan SA, Asiri AM, Al-Ghamdi NSM, Asad M, Zayed ME, Elroby SA, et al. Microwave assisted synthesis of chalcone and its polycyclic heterocyclic analogues as promising antibacterial agents: In vitro, in silico and DFT studies. Journal of Molecular Structure. 2019; 1190:77-85.

  • Ashok D, Ravi S, Ganesh A, Lakshmi BV, Adam S, Murthy S. Microwave-assisted synthesis and biological evaluation of carbazole-based chalcones, aurones and flavones. Medicinal Chemistry Research. 2016; 25(5):909-22.

  • Rahim M, Bhuiayan M, Matin M. Microwave assisted efficient synthesis of some flavones for antimicrobial and ADMET studies. Journal of Scientific Research. 2020; 12(4):673-85.

  • Kabalka GW, Mereddy AR. Microwave-assisted synthesis of functionalized flavones and chromones. Tetrahedron Letters. 2005; 46(37):6315-7.

  • Sarda SR, Jadhav WN, Pawar RP. I2-Al2O3: A suitable heterogeneous catalyst for the synthesis of flavones under microwave irradiation. Int J Chem Tech Res. 2009; 1(3):539-43.


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  • A Short Review on Synthetic Methodologies of Flavonoids

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Authors

Mufliha Murtaza
Department of Chemistry, Lahore Garrison University, Lahore, Pakistan
Affifa Tajammal
Department of Chemistry, Lahore Garrison University, Lahore, Pakistan
Muhammad Hamza Ashfaq
Department of Chemistry, School of Science, University of Management and Technology, Lahore, Pakistan
Waqar Mirza
Department of Chemistry, Lahore Garrison University, Lahore, Pakistan
Ansa Nazir
Department of Chemistry, Lahore Garrison University, Lahore, Pakistan
Iram Hanif
Department of Chemistry, Lahore Garrison University, Lahore, Pakistan

Abstract


Flavonoids are the pigments present in plants which mostly found in terrestrial plants. Flavonoids are indeed a naturally present group of polyphenolic compounds present in plants. They were driven by the term "flavus," which means "yellow." It is a 15-carbon skeleton compound. They have fused aromatic ring and benzopyran heterocyclic ring having oxygen atom in it along with phenyl substituent. They are synthesized from Phenylalanine. In cereals and Herbs, they are mainly found. Flavonoids are compounds that are biologically active. They provide color and protection from ultraviolet rays. They have many classes based upon oxidative status, number, and types of substituents present. Flavonoids exist naturally in the form of polymers, most commonly in dimers form. They occur primarily in β-glycosides form except for Catechins. They can help in the inhibition of enzymes and stimulate some hormones along with some neurotransmitters. They also show the properties of scavenging free radicals. They can inhibit or kill many bacterial strains, viral enzymes, and pathogenic protozoans. There are various techniques and methods for the synthesis of natural products artificially. In the present study, we have attempted to cover different synthetic methods for flavonoid synthesis to find its best way to synthesize. It was concluded that Baker & Venkatraman synthesis and Claisen-Schmidt condensation are well-known methods used to synthesize flavonoids.

Keywords


Flavonoids, Polyphenols, Phenylalanine, Baker & Venkatraman, Claisen-Schmidt

References