Generic placeholder image

Current Organic Chemistry


ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

General Review Article

An Overview of the Chemistry and Pharmacological Potentials of Furanones Skeletons

Author(s): Zahra Hosseinzadeh and Ali Ramazani*

Volume 23, Issue 14, 2019

Page: [1581 - 1599] Pages: 19

DOI: 10.2174/1385272823666190820111928

Price: $65


The furanone structure, a significant group of heterocyclic compounds, is frequently found in natural products that are exhibiting striking pharmacological effects and a growing field of research. They have a wide spectrum of pharmaceutical activity: anticataract, anticancer, antibacterial, anti-inflammatory, anticonvulsant. This review article presents a summary of natural furanones, synthetic methods, and the biological effects of these important compounds. Solid-phase method, cross-coupling reactions, Maillard-type reaction, the cycloaddition of alcohol and phenyl nitrile oxide, and side-chain modifications are some types of reactions for the preparation of furanone derivatives. Methods of preparation and pharmacological activities of furanone skeletons that are discussed in this review article will help the medicinal chemists to design and execute novel procedures towards finding new drugs.

Keywords: Heterocyclic, Furanone, Biological activity, Antimicrobial, Anticancer, Anti-cataract, Anti-inflammatory.

« Previous
Graphical Abstract
Arora, P.; Arora, V.; Lamba, H.; Wadhwa, D. Importance of heterocyclic chemistry: A review. Int. J. Pharm. Sci. Res., 2012, 3, 2947-2957.
Buntrock, R.E. The ACS Style Guide: Effective Communication of Scientific Information Edited by Anne M. Coghill and Lorrin R. Garson. American Chemical Society and Oxford University Press: Washington, DC and Oxford, UK 2006. ACS Publications., 2007.
Lattmann, E.; Sattayasai, N.; Schwalbe, C.S.; Niamsanit, S.; Billington, D.C.; Lattmann, P.; Langley, C.A.; Singh, H.; Dunn, S. Novel anti-bacterials against MRSA: Synthesis of focussed combinatorial libraries of tri-substituted 2(5H)-furanones. Curr. Drug Discov. Technol., 2006, 3(2), 125-134.
[] [PMID: 16925520]
Banskota, A.H.; Mcalpine, J.B.; Sørensen, D.; Aouidate, M.; Piraee, M.; Alarco, A-M.; Omura, S.; Shiomi, K.; Farnet, C.M.; Zazopoulos, E. Isolation and identification of three new 5-alkenyl-3,3(2H)-furanones from two streptomyces species using a genomic screening approach. J. Antibiot. (Tokyo), 2006, 59(3), 168-176.
[] [PMID: 16724457]
Koga, T.; Moro, K.; Matsudo, T. Antioxidative behaviors of 4-hydroxy-2, 5-dimethyl-3 (2 H)-furanone and 4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3 (2 H)-furanone against lipid peroxidation. J. Agric. Food Chem., 1998, 46(3), 946-951.
El-Tombary, A.A.; Abdel-Ghany, Y.S.; Belal, A.S.; El-Dine, S.A.S.; Soliman, F.S. Synthesis of some substituted furan-2 (5H)-ones and derived quinoxalinones as potential anti-microbial and anti-cancer agents. Med. Chem. Res., 2011, 20, 865-876.
Hoye, T.R.; Tan, L. Total synthesis of the potent antitumor, bis-tetrahydrofuranyl annonaceous acetogenins (+)-asimicin and (+)-bullatacin. Tetrahedron Lett., 1995, 36, 1981-1984.
Wu, Y-C.; Luo, S-H.; Mei, W-J.; Cao, L.; Wu, H-Q.; Wang, Z-Y. Synthesis and biological evaluation of 4-biphenylamino-5-halo-2(5H)-furanones as potential anticancer agents. Eur. J. Med. Chem., 2017, 139, 84-94.
[] [PMID: 28800460]
Wu, Y.C.; Cao, L.; Mei, W.J.; Wu, H.Q.; Luo, S.H.; Zhan, H.Y.; Wang, Z.Y. Bis-2(5H)-furanone derivatives as new anticancer agents: Design, synthesis, biological evaluation, and mechanism studies. Chem. Biol. Drug Des., 2018, 92(1), 1232-1240.
[] [PMID: 29469985]
Hanessian, S.; Park, H.; Yang, R-Y. Zinc-mediated allylation of N-protected α-amino aldehydes in aqueous solution. Stereoselective synthesis of phe-phe hydroxyethylene dipeptide isosteres. Synlett, 1997, 1997, 351-352.
Hanessian, S.; Park, H.; Yang, R-Y. Zinc-mediated allylation of N-protected α-amino aldehydes in aqueous solution. stereoselective synthesis of anti-and syn-β-amino alcohols with functionalized allyl groups. Synlett, 1997, 1997, 353-354.
Hashem, A.I.; Abou-Elmagd, W.S.; Abd-Elaziz, A. Synthesis and reactions of some 2 (3H)-and 2 (5H)-furanone. Eur. Chem. Bull., 2014, 3, 1064-1068.
Padakanti, S.; Pal, M.; Yeleswarapu, K.R. An improved and practical synthesis of 5, 5-dimethyl-3-(2-propoxy)-4-(4-methanesulfonylphenyl)-2-(5H)-furanone (DFP - a selective inhibitor of cyclooxygenase-2). Tetrahedron, 2003, 59, 7915-7920.
Klunk, W.E.; Covey, D.F.; Ferrendelli, J.A. Anticonvulsant properties of alpha, gamma, and alpha, gamma-substituted gamma-butyrolactones. Mol. Pharmacol., 1982, 22(2), 438-443.
[PMID: 7144736]
Hosseinzadeh, M.; Hossaini, Z.; Rostami‐Charati, F.; Vaseghi, S.; Rostamian, R. Synthesis of furanone derivatives using 15‐nonacosanole extracted from Fumaria officinalis in the presence of KF/clinoptilolite nanoparticles. J. Heterocycl. Chem., 2017, 54(5), 2767-2772.
El-Sayed, K.A.; Orabi, K.Y.; Dunbar, D.C.; Hamann, M.T.; Avery, M.A.; Sabnis, Y.A.; Mossa, J.S.; El-Feraly, F.S. Transformation of lactone to lactam in sarcophine and antimalarial activity of the resulting N-substituted azasarcophines. Tetrahedron, 2002, 58, 3699-3708.
Ngwane, A.H.; Panayides, J.L.; Chouteau, F.; Macingwana, L.; Viljoen, A.; Baker, B.; Madikane, E.; de Kock, C.; Wiesner, L.; Chibale, K.; Parkinson, C.J.; Mmutlane, E.M.; van Helden, P.; Wiid, I. Design, synthesis, and in vitro antituberculosis activity of 2(5H)-furanone derivatives. IUBMB Life, 2016, 68(8), 612-620.
[] [PMID: 27346745]
Gondela, E.; Walczak, K.Z. Synthesis and preliminary bioactivity assays of 3,4-dichloro-5-(ω-hydroxyalkylamino)-2(5H)-furanones. Eur. J. Med. Chem., 2010, 45(9), 3993-3997.
[] [PMID: 20573426]
Shin, S.S.; Byun, Y.; Lim, K.M.; Choi, J.K.; Lee, K-W.; Moh, J.H.; Kim, J.K.; Jeong, Y.S.; Kim, J.Y.; Choi, Y.H.; Koh, H.J.; Park, Y.H.; Oh, Y.I.; Noh, M.S.; Chung, S. In vitro structure-activity relationship and in vivo studies for a novel class of cyclooxygenase-2 inhibitors: 5-aryl-2,2-dialkyl-4-phenyl-3(2H)furanone derivatives. J. Med. Chem., 2004, 47(4), 792-804.
[] [PMID: 14761182]
Fujiwara, K.; Tsukamoto, H.; Izumikawa, M.; Hosoya, T.; Kagaya, N.; Takagi, M.; Yamamura, H.; Hayakawa, M.; Shin-Ya, K.; Doi, T. Total synthesis and structure determination of JBIR-108-A 2-Hydroxy-2-(1-hydroxyethyl)-2,3-dihydro-3(2H)-furanone isolated from Streptomyces gramineus IR087Pi-4. J. Org. Chem., 2015, 80(1), 114-132.
[] [PMID: 25437251]
Wei, M-X.; Zhang, J.; Ma, F-L.; Li, M.; Yu, J-Y.; Luo, W.; Li, X-Q. Synthesis and biological activities of dithiocarbamates containing 2(5H)-furanone-piperazine. Eur. J. Med. Chem., 2018, 155, 165-170.
[] [PMID: 29886320]
Ramach, C.S.; Sreekumar, P.; Pillai, P.M.; Balaram, P. Synthesis and cytotoxicity studies of some furanone derivatives. Org.Chem: India. J., 2012, 8
Nagarapu, L.; Kumar, U.N.; Upendra, P.; Bantu, R. Simple, convenient method for the synthesis of substituted furan-2 (5H)-one derivatives using tin (II) chloride. Synth. Commun., 2012, 42, 2139-2148.
Rappai, J.P.; Raman, V.; Unnikrishnan, P.A.; Prathapan, S.; Thomas, S.K.; Paulose, C.S. Preliminary investigations on the synthesis and antitumor activity of 3(2H)-furanones. Bioorg. Med. Chem. Lett., 2009, 19(3), 764-765.
[] [PMID: 19121938]
Ramazani, A.; Reza Kazemizadeh, A. Preparation of stabilized phosphorus ylides via multicomponent reactions and their synthetic applications. Curr. Org. Chem., 2011, 15, 3986-4020.
Azizmohammadi, M.; Khoobi, M.; Ramazani, A.; Emami, S.; Zarrin, A.; Firuzi, O.; Miri, R.; Shafiee, A. 2H-chromene derivatives bearing thiazolidine-2,4-dione, rhodanine or hydantoin moieties as potential anticancer agents. Eur. J. Med. Chem., 2013, 59, 15-22.
[] [PMID: 23202485]
Ramazani, A.; Khoobi, M.; Torkaman, A.; Nasrabadi, F.Z.; Forootanfar, H.; Shakibaie, M.; Jafari, M.; Ameri, A.; Emami, S.; Faramarzi, M.A.; Foroumadi, A.; Shafiee, A. One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl) methanamines. Eur. J. Med. Chem., 2014, 78, 151-156.
[] [PMID: 24681979]
Dayyani, N.; Khoee, S.; Ramazani, A. Design and synthesis of pH-sensitive polyamino-ester magneto-dendrimers: Surface functional groups effect on viability of human prostate carcinoma cell lines DU145. Eur. J. Med. Chem., 2015, 98, 190-202.
[] [PMID: 26021708]
Malekzadeh, M.A.; Ramazani, A.; Tabatabaei Rezaei, S.J.; Niknejad, H. Design and construction of multifunctional hyperbranched polymers coated magnetite nanoparticles for both targeting magnetic resonance imaging and cancer therapy. J. Colloid Interface Sci., 2017, 490, 64-73.
[] [PMID: 27870961]
Husain, A.; Alam, M.M.; Hasan, S.M.; Yar, M.S. 2(3H)-furanones and 2(3H)-pyrrolones: Synthesis and antimycobacterial evaluation. Acta Pol. Pharm., 2009, 66(2), 173-180.
[PMID: 19719052]
Sampson, P.; Roussis, V.; Drtina, G.J.; Koerwitz, F.L.; Wiemer, D.F. The intramolecular Wadsworth-Emmons condensation of. gamma-(acyloxy)-. beta.-ketophosphonates. A new route to 3 (2H)-furanones. J. Org. Chem., 1986, 51, 2525-2529.
Chatani, N.; Morimoto, T.; Fukumoto, Y.; Murai, S. Ru3 (CO) 12-catalyzed cyclocarbonylation of yne-aldehydes to bicyclic α, β-Unsaturated γ-butyrolactones. J. Am. Chem. Soc., 1998, 120, 5335-5336.
Schönberg, A.; Mustafa, A. Dehydrogenation reactions by the action of free radicals. J. Am. Chem. Soc., 1951, 73, 2401-2401.
Tanabe, Y.; Mitarai, K.; Higashi, T.; Misaki, T.; Nishii, Y. Efficient one-step synthesis of trialkylsubstituted 2 (5H)-furanones utilizing direct Ti-crossed aldol condensation and its application to the straightforward synthesis of (R)-mintlactone and (R)-menthofuran. Chem. Commun. (Camb.), 2002, 21, 2542-2543.
Inagaki, S.; Nakazato, M.; Fukuda, N.; Tamura, S.; Kawano, T. Synthesis of 4-Halo-3(2H)-furanones using intramolecular cyclization of sulfonium salts. J. Org. Chem., 2017, 82(11), 5583-5589.
[] [PMID: 28493722]
Krauser, S.F.; Watterson, A.C., Jr New mild conditions for the synthesis of. alpha., beta.-unsaturated. gamma.-lactones. beta.-(2-Phthalimidoethyl)-. DELTA. alpha., beta.-butenolide. J. Org. Chem., 1978, 43, 3400-3402.
Curran, D.P.; Singleton, D.H. Reduction of Δ2-isoxazolines-2. A facile synthesis of 3 (2H)-furanones. Tetrahedron Lett., 1983, 24, 2079-2082.
Roscher, R.; Schreier, P.; Schwab, W. A facile synthesis of 2, 5‐dimethyl‐4‐hydroxy‐3 (2H)‐furanone [2‐(or 5‐) methyl 14C](furaneol [2‐(or 5‐) methyl 14C]). J. Labelled Comp. Radiopharm., 1997, 39, 493-499.
Roscher, R.; Schreier, P.; Schwab, W. Metabolism of 2, 5-dimethyl-4-hydroxy-3 (2H)-furanone in detached ripening strawberry fruits. J. Agric. Food Chem., 1997, 45, 3202-3205.
Newman, L.M.; Garcia, H.; Hudlicky, T.; Selifonov, S.A. Directed evolution of the dioxygenase complex for the synthesis of furanone flavor compounds. Tetrahedron, 2004, 60, 729-734.
Kirsch, S.F.; Binder, J.T.; Liébert, C.; Menz, H. Gold(III)- and platinum(II)-catalyzed domino reaction consisting of heterocyclization and 1,2-migration: Efficient synthesis of highly substituted 3(2H)-furanones. Angew. Chem. Int. Ed. Engl., 2006, 45(35), 5878-5880.
[] [PMID: 16871607]
Nardini, V.; Machado Rodrigues, S.M.; Constantino, M.G.; da Silva, G.V. Side-chain modifications of highly functionalized 3(2H)-furanones. Molecules, 2012, 17(10), 12151-12162.
[] [PMID: 23085662]
Langer, P.; Krummel, T. Chemo-and regio-selective synthesis of functionalized 3 (2H)-furanones by the first cyclization reactions of 1, 3-bis (trimethylsiloxy) buta-1, 3-dienes with α-chlorocarboxylic acid chlorides. Chem. Commun. (Camb.), 2000, 11, 967-968.
Padmapriya, A.A.; Just, G.; Lewis, N.G. Synthesis of 3-chloro-4-(dichloromethyl)-5-hydroxy-2 (5H)-furanone, a potent mutagen. Can. J. Chem., 1985, 63, 828-832.
Hiyama, T.; Oishi, H.; Suetsugu, Y.; Nishide, K.; Saimoto, H. Synthesis of 4-Amino-2 (5H)-furanones through intra-and intermolecular nitrile addition of ester enolates. Construction of carbon framework of an antitumor antibiotic basidalin. Bull. Chem. Soc. Jpn., 1987, 60, 2139-2150.
Watanabe, M.; Tsukazaki, M.; Hirkawa, Y.; Iwao, M.; Furukawa, S. An efficient synthesis of 2 (5H)-Furanone and furan derivatives using 3-(Phenylthio) propenal as a 1, 3-Dipolar Synthon. Chem. Pharm. Bull. (Tokyo), 1989, 37, 2914-2919.
Arayarat, P.; Singh, H.; Lattmann, E. Solid phase synthesis of substituted 4-amino-5-hydroxy-2 (5H)-furanones. Sci. Asia, 2001, 27, 121-125.
Wu, J.; Zhu, Q.; Wang, L.; Fathi, R.; Yang, Z. Palladium-catalyzed cross-coupling reactions of 4-tosyl-2(5H)-furanone with boronic acids: A facile and efficient route to generate 4-substituted 2(5H)-furanones. J. Org. Chem., 2003, 68(2), 670-673.
[] [PMID: 12530910]
Hjelmgaard, T.; Persson, T.; Rasmussen, T.B.; Givskov, M.; Nielsen, J. Synthesis of furanone-based natural product analogues with quorum sensing antagonist activity. Bioorg. Med. Chem., 2003, 11(15), 3261-3271.
[] [PMID: 12837536]
Grossmann, G.; Jolivet, B.; Bornand, M.; Séquin, U.; Spindler, K-D. Synthesis and biological evaluation of some furanones as putative chitinase inhibitors. Synthesis, 2005, 2005, 1543-1549.
Murthy, S.N.; Madhav, B.; Kumar, A.V.; Rao, K.R.; Nageswar, Y. Facile and efficient synthesis of 3, 4, 5-substituted furan-2 (5H)-ones by using β-cyclodextrin as reusable catalyst. Tetrahedron, 2009, 65, 5251-5256.
Surmont, R.; Verniest, G.; De Kimpe, N. Short synthesis of the seed germination inhibitor 3,4,5-trimethyl-2(5H)-furanone. J. Org. Chem., 2010, 75(16), 5750-5753.
[] [PMID: 20704450]
Tan, Y-H.; Li, J-X.; Xue, F-L.; Qi, J.; Wang, Z-Y. Concise synthesis of chiral 2 (5H)-furanone derivatives possessing 1, 2, 3-triazole moiety via one-pot approach. Tetrahedron, 2012, 68, 2827-2843.
Luo, S-H.; Xiong, J-F.; Wang, Z-Y.; Mo, G-Z. Design and synthesis of 2 (5H)-furanone liquid-crystal compounds based on natural molecules and biphenyl derivatives. Res. Chem. Intermed., 2013, 39, 1865-1876.
Kangani, M.; Hazeri, N.; Maghsoodlou, M-T. Synthesis of pyrrole and furan derivatives in the presence of lactic acid as a catalyst. J. Saudi Chem. Soc., 2017, 21, 160-164.
Ma, S.; Shi, Z. Pd(0)/Ag(+)-cocatalyzed cyclization reaction of 1,2-allenic carboxylic acids with aryl/alkenyl halides. An efficient synthesis of butenolides. J. Org. Chem., 1998, 63(18), 6387-6389.
[] [PMID: 11672274]
Patil, J.; Kenny, R.; Mashelkar, B.; Mashelkar, U. Studies of 4-furanone and 4-oxazolone substituted coumarins: Synthesis, physiological and biological activity. Available at:.
Nair, V.; Mathew, S.C.; Vellalath, S.; Pillai, A.N.; Suresh, E. An Efficient three-component reaction involving triazolylidene carbene, DMAD, and aldehydes for the synthesis of furanone derivatives. Synthesis, 2008, 2008, 551-554.
Varghese, B.; Al-Busafi, S.N.; Suliman, F.O.; Al-Kindy, S.M. 3 (2H)-Furanone as a promising scaffold for the synthesis of novel fluorescent organic dyes: An experimental and theoretical investigation. N J. Chem., 2015, 39, 6667-6676.
Shiozawa, H.; Takahashi, M.; Takatsu, T.; Kinoshita, T.; Tanzawa, K.; Hosoya, T.; Furuya, K.; Takahashi, S.; Furihata, K.; Seto, H. Trachyspic acid, a new metabolite produced by Talaromyces trachyspermus, that inhibits tumor cell heparanase: Taxonomy of the producing strain, fermentation, isolation, structural elucidation, and biological activity. J. Antibiot. (Tokyo), 1995, 48(5), 357-362.
[] [PMID: 7797435]
Paul, M.C.; Zubía, E.; Ortega, M.J.; Salvá, J. New polypropionates from Siphonaria pectinata. Tetrahedron, 1997, 53, 2303-2308.
Lattmann, E.; Kinchington, D.; Dunn, S.; Singh, H.; Ayuko, W.O.; Tisdale, M.J. Cytotoxicity of 3,4-dihalogenated 2(5H)-furanones. J. Pharm. Pharmacol., 2004, 56(9), 1163-1170.
[] [PMID: 15324485]
Wu, H.; Song, Z.; Hentzer, M.; Andersen, J.B.; Molin, S.; Givskov, M.; Høiby, N. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J. Antimicrob. Chemother., 2004, 53(6), 1054-1061.
[] [PMID: 15117922]
Manefield, M.; Welch, M.; Givskov, M.; Salmond, G.P.; Kjelleberg, S. Halogenated furanones from the red alga, Delisea pulchra, inhibit carbapenem antibiotic synthesis and exoenzyme virulence factor production in the phytopathogen Erwinia carotovora. FEMS Microbiol. Lett., 2001, 205(1), 131-138.
[] [PMID: 11728727]
Ramachandran, C.S.; Sreekumar, P. Synthesis, characterisation and antibacterial evaluation of 2 (5h) furanone derivatives from highly functionalised mucobromic acid. Int. J. Pharm. Pharm. Sci., 2011, 3, 225-228.
Huff, T.; Kuball, H-G.; Anke, T. 7-Chloro-4,6-dimethoxy-1(3H)-isobenzofuranone and basidalin: Antibiotic secondary metabolites from Leucoagaricus carneifolia gillet (basidiomycetes).[corrected] Z. Natforsch. C J. Biosci., 1994, 49(7-8), 407-410.
[ 10.1515/znc-1994-7-803] [PMID: 7945669]
Sasaki, T.; Yamakoshi, J.; Saito, M.; Kasai, K.; Matsudo, T.; Kikuchi, M.; Koga, T.; Mori, K. Synthesis of 4-hydroxy-3(2H)-furanone acyl derivatives and their anti-cataract effect on spontaneous cataract rats (ICR/f). Biosci. Biotechnol. Biochem., 1998, 62(11), 2145-2154.
[] [PMID: 9972235]
Takao, K-I.; Ochiai, H.; Yoshida, K-I.; Hashizuka, T.; Koshimura, H.; Tadano, K-I.; Ogawa, S. Novel total synthesis of (+)-eremantholide A. J. Org. Chem., 1995, 60, 8179-8193.
Le-Quesne, P.W.; Menachery, M.D.; Pastore, M.P.; Kelley, C.J.; Brennan, T.F.; Onan, K.D.; Raffauf, R.F.; Weeks, C.M. Antitumor plants. 12. Further sesquiterpenoid constituents of Lychnophora affinis Gardn. (Compositae). X-ray structure analysis of lychnophorolide A. J. Org. Chem., 1982, 47, 1519-1521.
Midland, S.L.; Keen, N.T.; Sims, J.J. Secosyrins 1 and 2 and syributins 1 and 2: Novel structures produced by bacteria expressing the avrD gene. J. Org. Chem., 1995, 60, 1118-1119.
Miao, S.; Andersen, R.J.; Rubrolides, A.H. metabolites of the colonial tunicate Ritterella rubra. J. Org. Chem., 1991, 56, 6275-6280.
Ortega, M.J.; Zubía, E.; Ocaña, J.M.; Naranjo, S.; Salvá, J. New rubrolides from the ascidian Synoicum blochmanni. Tetrahedron, 2000, 56, 3963-3967.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy