Chalcones: Retrospective Synthetic Approaches and Mechanistic Aspects of a Privileged Scaffold

Author(s): Emília P.T. Leitão*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 24 , 2020

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This review summarizes the synthetic methodologies used in the last 25 years for the synthesis of chalcones, which are a class of flavonoids having a 1,3-diphenyl-2-propene-1-one backbone. These compounds are considered a hot topic in the field of medicinal chemistry, due to their pharmacological activity and because they are important precursors for the synthesis of heterocyclic compounds with therapeutic applications such as: flavones, flavanones, isoxazolines, benzothiazepines, pyrimidines and pyrazolines derivatives.

Keywords: Chalcones, scaffold, medicinal chemistry, pharmacological activity, flavones, flavanones, isoxazolines, benzothiazepines, pyrimidines, pyrazolines derivatives.

Batovska DI, Todorova IT. Trends in utilization of the pharmacological potential of chalcones. Curr Clin Pharmacol 2010; 5(1): 1-29.
[] [PMID: 19891604]
Fayed TA. A novel chalcone-analogue as an optical sensor based on ground and excited states intramolecular charge transfer: a combined experimental and theoretical study. Chem Phys 2006; 324(2-3): 631-8.
Gupta D, Jaın DK, Trıvedı P. Recent advances in chalcones as antinfective agents. Chem Sci Int J 2010; 8(1): 649-54.
Sahu NK, Balbhadra SS, Choudhary J, Kohli DV. Exploring pharmacological significance of chalcone scaffold: a review. Curr Med Chem 2012; 19(2): 209-25.
[] [PMID: 22320299]
Iwashina T. The structure and distribution of the flavonoids in plants. J Plant Res 2000; 113(3): 287-99.
Tomas-Barberan FA, Clifford MN. Review Flavanones, chalcones and dihydrochalcones - nature, occurrence and dietary burden. J Sci Food Agric 2000; 80(7): 1073-80.
Katrizky AR, Rees CW. Comprehensive Heterocyclic Chemistry. Oxford: Pergamon Press 1984; Vol. 2 and 4.
DuBois GE, Crosby GA, Stephenson RA, Wingard RE Jr. Dihydrochalcone sweeteners. Synthesis and sensory evaluation of sulfonate derivatives. J Agric Food Chem 1977; 25(4): 763-72.
[] [PMID: 881496]
Singh N, Ahmad S, Alam MS. Biological potentials of chalcone: a review. Int 349 J Pharm Biol Arch 2012; 3(6): 1298-303.
Albuquerque HMT, Santos CMM, Cavaleiro JAS, Silva AMS. Chalcones as versatile synthons for the synthesis of 5- and 6-membered nitrogen heterocycles. Curr Org Chem 2014; 18(6): 2750-75.
Jin C, Liang YJL, He H, Fu L. Synthesis and antitumor activity of novel chalcone derivatives. Biomed Pharmacother 2013; 67(3): 215-7.
[] [PMID: 23478573]
Habib SI. Chemical and biological potential of chalcones as a source of drug: a review. IJPPR Human 2018; 11(2): 104-18.
Zhong P, Wu L, Qian Y, et al. Blockage of ROS and NF-κB-mediated inflammation by a new chalcone L6H9 protects cardiomyocytes from hyperglycemia-induced injuries. Biochim Biophys Acta 2015; 1852(7): 1230-41.
[] [PMID: 25736300]
Wu X, Wilairat P, Go ML. Antimalarial activity of ferrocenyl chalcones. Bioorg Med Chem Lett 2002; 12(17): 2299-302.
[] [PMID: 12161120]
Xu HX, Wan M, Dong H, But PPH, Foo LY. Inhibitory activity of flavonoids and tannins against HIV-1 protease. Biol Pharm Bull 2000; 23(9): 1072-6.
[] [PMID: 10993207]
Nakagawa G, Lee K. Anti-AIDS agents 68. The first total synthesis of a unique potent anti-HIV chalcone from genus Desmos. Tetrahedron Lett 2006; 47: 8263-6.
Won SJ, Liu CT, Tsao LT, et al. Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur J Med Chem 2005; 40(1): 103-12.
[] [PMID: 15642415]
El Sayed Aly MR, Abd El Razek Fodah HH, Saleh SY. Antiobesity, antioxidant and cytotoxicity activities of newly synthesized chalcone derivatives and their metal complexes. Eur J Med Chem 2014; 76: 517-30.
[] [PMID: 24602794]
Lawrence NJ, McGown AT, Ducki S, Hadfield JA. The interaction of chalcones with tubulin. Anticancer Drug Des 2000; 15(2): 135-41.
[PMID: 10901301]
Rao GS, Kalaichelvan VK, Rao GS. Synthesis and antidepressant activity of certain chalcones and chalcone based simple pyrazolines. J Pharm Sci. &. Res 2015; 7(9): 676-80.
Sashidhara KV, Kumar M, Kumar A. A novel route to synthesis of flavones from salicylaldehyde and acetophenone derivatives. Tetrahedron Lett 2012; 53(18): 2355-9.
Albogami AS, Karama U, Mousa AA, Khan M, Al-Mazroa SA, Alkhathlan HZ. Simple and efficient one step synthesis of functionalized flavanones and chalcones. Orient J Chem 2012; 28(2): 619-26.
Jayashree BS, Noor FA, Yogendra N, Kumar DV. Synthesis of substituted 3-hydroxy flavones for antioxidant and antimicrobial activity. Pharmacol Online 2008; 3: 586-95.
Sunee KK, Reddy KT, Vamsikanth A, Omprakash G, Dubey PK. Synthesis and characterization of some novel isoxazoles via chalcone intermediates. Pharma Chem 2011; 3(5): 113-22.
Chate AV, Joshi RS, Mandhane PG, Gil CH. An Improved procedure for the synthesis of 1,5-benzothiazepines using ceric ammonium nitrate (CAN). J Korean Chem Soc 2011; 55(5): 776-80.
Ma Y, Zang Y. o-Nitroanilines and chalcones induced by low-valent titanium. Synth Commun 2002; 32(2): 165-9.
Faldu VJ, Gothalia VK, Shab VH. Characterization and antitubercular activity of synthesized pyrimidine drivatives via chalcones. Indian J Chem 2015; ((Sec B)): 391-8.
Kendre MM, Baseer MA. Synthesis and evaluation of some new pyrazoline derivatives as antimicrobial agents. Orient J Chem 2013; 29(1): 253-6.
Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR. Vogel’s Textbook of Practical Organic Chemistry 5th ed. 1989; 1034.
Dhar DN, Lal JB. Chalcones. Condensation of aromatic aldehydes with resacetophenone. J Org Chem 1958; 23(8): 1159-61.
Davey W, Gwilt JR. 196 Chalcones and related compounds. Part I. Preparation of nitro-, amino-, and halogeno-chalcones. J Chem Soc 1957; 12: 1008-14.
Mukherji SM, Singh SP, Kapoor RP. Organic chemistry vol II In: International (P) Limited. 2003; p. 586.
Jun N, Hong G, Jun K. Synthesis and evaluation of 2′,4′,6′-trihydroxychalcones as a new class of tyrosinase inhibitors. Bioorg Med Chem 2007; 15(6): 2396-402.
[] [PMID: 17267225]
Beom-Tae K, Kwang-Joong O, Jae-Chul C, Ki-Jun H. Synthesis of dihydroxylated chalcone derivatives with diverse substitution patterns and their radical scavenging ability toward DPPH free radicals. Bull Korean Chem Soc 2008; 29(6): 1125-30.
Ha ST, Low YW. Synthesis and Phase Transition behaviours of new chalcone derivatives. J Chem 2013; 2013 943723
Da Costa RGM, Farias FRL, Maqueira L, et al. Synthesis, photophysical and electrochemical properties of novel D-π-D and D-π-A triphenylamino-chalcones and β-arylchalcones. J Braz Chem Soc 2019; 30(1): 81-9.
Jayapal MR, Prasad KS, Sreedhar NY. Synthesis and characterization of 2,6-dihydroxy substituted chalcones using PEG-400 as a recyclable solvent. J Pharm Sci & Res 2010; 2(8): 450-8.
Leitão EPT. Preparação de nafto-flavonoides com potencial aplicação terapêutica.Doctorial dissertation. 2015.
Elfi Susanti VH, Setyowati WAE. A Green Synthesis of chalcones as an antioxidant and anticancer. IOP Conf Ser Mater Sci Eng. 299
Dhananjayulu M, Prasad MS, Swarupa C. Synthesis characterisation and electrochemical behaviour of 2-hydroxy chalcones using silicagel supported piperidine. Int J Innovative Res Eng Tech 2014; 3(5)
Bhagat S, Sharma R, Sawant DM, Sharma L, Chakraborti AK. LiOH•H2O as a novel dual activation catalyst for highly efficient and easy synthesis of 1,3-diaryl-2-propenones by Claisen-Schmidt condensation under mild conditions. J Mol Catal Chem 2006; 244(1-2): 20-4.
Kantam ML, Prakash BV, Reddy CV. Efficient synthesis of chalcones by a solid base catalyst. Synth Commun 2005; 35(14): 1971-8.
Saravanamurugan S, Palanichamy M, Arabindoo B, Murugesan V. Solvent free synthesis of chalcone and flavanone over zinc oxide supported metal oxide catalysts. Catal Commun 2005; 6(6): 399-403.
Basaif SA, Sobahi TR. Stereoselective crossed-aldol condensation of some active methylene compounds with aromatic aldehydes in aqueous medium. Synthesis of (2E)-1,3-disubstituted propenones. Magalat Game’at al-Malik Abdul Aziz Al-U’lum 2005; 17(1): 107-16.
Narender T, Reddy KP. A simple and highly efficient method for the synthesis of chalcones by using borontrifluoride-etherate. Tetrahedron Lett 2007; 48(18): 3177-80.
Kumar D, Sandhu S, Sandhu JS. An efficient green protocol for the synthesis of chalcones by a Claisen-Schmit reaction using bismuth (III) chloride as a catalyst under solvent-free condition. Green Chem Lett Rev 2010; 3(4): 283-6.
Ramesh G, Sunil J, Pramod K. Methane sulphonic acid catalyzed efficient protocol for synthesis of 2-hydroxy chalcones. Org Chem Ind J 2016; 12(3): 1-8.
Sultan A, Raza AR, Abbas M, Khan KM, Tahir MN, Saari N. Evaluation of silica-H2SO4 as an efficient heterogeneous catalyst for the synthesis of chalcones. Molecules 2013; 18(8): 10081-94.
[] [PMID: 23966089]
Devi DL, Aswini R, Kothai S. Synthesis and characterisation of chalcone based copolyesters and their anticancer activity. IJPSR 2018; 9(4): 1589-93.
Rueping M, Bootwicha T, Baars H, Sugiono E. Continuous-flow hydration-condensation reaction: Synthesis of α,β-unsaturated ketones from alkynes and aldehydes by using a heterogeneous solid acid catalyst. Beilstein J Org Chem 2011; 7(1): 1680-7.
[] [PMID: 22238547]
Chen D, Li Y. New method for synthesizing alpha, betaunsaturated carbonyl compound via one-pot condensation Chinese patents CN102786371. 2011.
Xu LW, Li L, Xia CG, Zhao PQ. Efficient coupling reactions of arylalkynes and aldehydes leading to the synthesis of enones. Helv Chim Acta 2004; 87(12): 3080-4.
Chemler SR, Trauner D, Danishefsky SJ. The β-alkyl suzubi-Miyaura cross-coupling reaction: development mechanistic study, and applications in natural product synthesys. Angew Chem Int Ed 2001; 40(24): 4544-68.
[<4544:AID-ANIE4544>3.0.CO;2-N] [PMID: 12404358]
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.
Al-Masum M. Ng, Wai MC. Palladium-catalyzed direct cross-coupling of potassium styryltrifluoroborates and benzoyl chlorides-a one step method for chalcone synthesis. Tetrahedron Lett 2011; 52(9): 1008-10.
Xin BW. Synthesis of aryl ketones by cross-coupling reaction of arylboronic acids with carboxylic anhydrides in aqueous phase. Synth Commun 2008; 38(16): 2826-37.
Bianco A. Cavarischia., Farina A, Guiso M, Marra C. A new synthesis of flavonoids via Heck reaction. Tetrahedron Lett 2003; 44(51): 9107-9.
Wu XF, Neumann H, Spannenberg A, Schulz T, Jiao H, Beller M. Development of a general palladium-catalyzed carbonylative Heck reaction of aryl halides. J Am Chem Soc 2010; 132(41): 14596-602.
[] [PMID: 20866089]
Kumar A, Sharma S, Tripathi VD, Srivastava S. Synthesis of chalcones and flavanones using Julia-Kocienski olefination. Tetrahedron Lett 2010; 66(48): 9445-9.
Xu C, Chen G, Huang X. Chalcones by the Wittig reaction of a stable ylide with aldehydes under microwave irradiation. Org Prep Proced Int 1995; 27(5): 559-61.
Mason TJ, Cobley AJ, Graves JE, Morgan D. New evidence for the inverse dependence of mechanical and chemical effects on the frequency of ultrasound. Ultrason Sonochem 2011; 18(1): 226-30.
[] [PMID: 20605105]
Leonelli C, Mason TJ. Microwave and ultrasonic processing: now a realistic option for industry. Chem Eng Processing: Process Intensification 2010; 49(9): 885-900.
Cravotto G, Cintas P. Power ultrasound in organic synthesis: moving cavitational chemistry from academia to innovative and large-scale applications. Chem Soc Rev 2006; 35(2): 180-96.
[] [PMID: 16444299]
Lindy J, Lorimer JP, Mason TJ. Enhancement of an Ullmann coupling reaction induced by ultrasound. Ultrasonics 1986; 24(5): 292-3.
Jadidi K, Gharemanzadeh R, Mehrdad M, Darabi HR, Khavasi HR, Asgari D. A facile synthesis of novel pyrrolizidines under classical and ultrasonic conditions. Ultrason Sonochem 2008; 15(2): 124-8.
[] [PMID: 17475534]
Li JT, Yang WZ, Wang SX, Li SH, Li TS. Improved synthesis of chalcones under ultrasound irradiation. Ultrason Sonochem 2002; 9(5): 237-9.
[] [PMID: 12371199]
Calvino V, Picallo M, López-Peindo AJ, Martin-Aranda RM, Durán-Valle CJ. Ultrasound accelerated Claisen-Schmidt condensation: a green route to chalcones. J Appl Surf Sci 2006; 252(17): 6071-4.
Elizabeth PR, Rosa MM, Casa lB, et al. Sonocatalysis in solvent free conditions: an efficient eco-friendly methodology to prepare chalcones using a new type of aminografted zeolites. Catal Today 2006; 114: 183-7.
Younis A, Fathy U, El-kateb AA, Awad HM. Ultrasonic assisted synthesis of novel anticancer chalcones using water as green solvent. Pharma Chem 2016; 8(17): 129-36.
Reddy GV, Maitraie D, Narsaiah B, Rambabu Y, Rao PS. Microwave assisted knoevenagel condensation: a facile method for the synthesis of chalcones. Synth Commun 2001; 31(18): 2881-4.
Tiwari V, Ali P, Meshram J. Microwave Assisted Synthesis of 3-(2-chloroquiolin-3-yl)-1-substituted phenyl prop-2-en-1-ones Using K2CO3 as a mild, cheap and inexpensive catalyst. Int J Chemtech Res 2010; 2(2): 1031-5.
Jayapal MR, Sreedhar NY. Anhydrous K2CO3 as Catalyst for the synthesis of chalcones under microwave Irradiation. J Pharm Sci & Res 2010; 2(10): 644-7.
Jayapal MR, Sreedhar NY. Synthesis and characterization of 4 hydroxy chalcones by aldol condensation using SOCl2/EtOH. Int J Curr Pharm Res 2010; 2(4): 60-2.
Janaki P, Sekar KG, Thirunarayanan G. Microwave assisted sulphated titania catalyzed aldol condensation: synthesis of some (E) 3-(2-naphthyl)- 1-(substituted phenyl)-2-propen-1-ones under solvent-free conditions. Int Lett Chemi. Phys Astronomy 2014; 28(9): 16-22.
Braun RU, Ansorge M, Müller TJJ. Coupling-isomerization synthesis of chalcones. Chemistry 2006; 12(35): 9081-94.
[] [PMID: 16953503]

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Article Details

Year: 2020
Published on: 21 July, 2020
Page: [2843 - 2858]
Pages: 16
DOI: 10.2174/1381612826666200403124259
Price: $65

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