Abstract
Diphenyl ethers (DPE) and its analogs have exhibited excellent potential for therapeutic and industrial applications. Since the 19th century, intensive research is perpetuating on the synthetic routes and biological properties of DPEs. Few well-known DPEs are Nimesulide, Fenclofenac, Triclosan, Sorafenib, MK-4965, and MK-1439 which have shown the potential of this moiety as a lead scaffold for different pharmacological properties. In this review, we recapitulate the diverse synthetic route of DPE moiety inclusive of merits and demerits over the classical synthetic route and how this moiety sparked an interest in researchers to discern the SAR (Structure Activity Relationship) for the development of diversified biological properties of DPEs such as antimicrobial, antifungal, antiinflammatory & antiviral activities.
Keywords: Ullmann ether synthesis, diphenyl oxide, triclosan, dowtherm, nimesulide, enoyl-acyl carrier protein.
Graphical Abstract
[1]
Rahman, F.; Langford, K.H.; Scrimshaw, M.D.; Lester, J.N. Polybrominated Diphenyl Ether (PBDE) Flame Retardants. Sci. Total Environ., 2001, 275(1-3), 1-17.
[2]
Cabaleiro, D.; Pastoriza-Gallego, M.J.; Piñeiro, M.M.; Legido, J.L.; Lugo, L. Thermophysical properties of (Diphenyl Ether + Biphenyl) mixtures for their use as heat transfer fluids. J. Chem. Thermodyn., 2012, 50, 80-88.
[3]
Tait, S.; Perugini, M.; La Rocca, C. Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data. Food Chem. Toxicol., 2017, 108, 74-84.
[4]
Lu, S.Y.; Hamerton, I. Recent developments in the chemistry of halogen-free flame retardant polymers; Prog. Polymer Sci: Oxford, 2002, pp. 1661-1712.
[5]
Deasy, C.L. The chemistry of phenoxathiin and its derivatives. Chem. Rev., 1943, 32(2), 173-194.
[7]
Heath, R.J.; Rubin, J.R.; Holland, D.R.; Zhang, E.; Snow, M.E.; Rock, C.O. Mechanism of triclosan inhibition of bacterial fatty acid synthesis. J. Biol. Chem., 1999, 274(16), 11110-11114.
[8]
Hargreaves, J.; Park, J.O.; Ghisalberti, E.L.; Sivasithamparam, K.; Skelton, B.W.; White, A.H. New chlorinated diphenyl ethers from an aspergillus species. J. Nat. Prod., 2002, 65, 7-10.
[9]
Stermitz, F.R.; Schroeder, H.A.; Geigert, J. Asterric acid from scytalidium. Phytochemistry, 1973, 12(5), 1173.
[10]
Lee, H.J.; Lee, J.H.; Hwang, B.Y.; Kim, H.S.; Lee, J.J. Fungal metabolites, asterric acid derivatives inhibit Vascular Endothelial Growth Factor (VEGF)-Induced tube formation of HUVECs. J. Antibiot. (Tokyo), 2002, 55(6), 552-556.
[11]
Oh, H.; Kwon, T.O.; Gloer, J.B.; Marvanová, L.; Shearer, C.A. Tenellic acids A-D: New bioactive diphenyl ether derivatives from the aquatic fungus dendrospora tenella. J. Nat. Prod., 1999, 62(4), 580-583.
[12]
Lindley, J. Tetrahedron Report Number 163. Copper assisted nucleophilic substitution of Aryl halogen. Tetrahedron, 1984, 40(9), 1433-1456.
[13]
Ullmann, F. On a new mode of formation of diphenylamine derivatives. Chem. Ber., 1903, 36, 2382-2384.
[16]
Mann, G.; Hartwig, J.F. Nickel- vs Palladium-Catalyzed synthesis of protected phenols from Aryl halides. J. Org. Chem., 1997, 62(16), 5413-5418.
[17]
Widenhoefer, R.A.; Zhong, H.A.; Buchwald, S.L. Direct Observation of C-O reductive elimination from Palladium Aryl alkoxide complexes to form Aryl Ethers. J. Am. Chem. Soc., 1997, 119(29), 6787-6795.
[18]
Chen, G.; Chan, A.S.C.; Kwong, F.Y. Palladium-Catalyzed C-O bond formation: Direct synthesis of phenols and aryl/alkyl ethers from activated Aryl halides. Tetrahedron Lett., 2007, 48(3), 473-476.
[19]
Burgos, C.H.; Barder, T.E.; Huang, X.; Buchwald, S.L. Significantly improved method for the Pd-Catalyzed coupling of phenols with Aryl halides: Understanding ligand effects. Angew. Chem. Int. Ed., 2006, 45(26), 4321-4326.
[20]
Marcoux, J.F.; Doye, S.; Buchwald, S.L. A general copper-catalyzed synthesis of diaryl ethers. J. Am. Chem. Soc., 1997, 119(43), 10539-10540.
[21]
Ma, D.; Cai, Q.N. N-Dimethyl Glycine-Promoted ullmann coupling reaction of phenols and Aryl halides. Org. Lett., 2003, 5(21), 3799-3802.
[22]
Zou, B.; Yuan, Q.; Ma, D. Synthesis of 1,2-Disubstituted benzimidazoles by a cu-catalyzed Cascade Aryl amination/ condensation process. Angew. Chem. Int. Ed., 2007, 46(15), 2598-2601.
[23]
Lv, X.; Bao, W. A β-Keto Ester as a novel, efficient, and versatile ligand for Copper(I)-Catalyzed C-N, C-O, and C-S coupling reactions. J. Org. Chem., 2007, 72(10), 3863-3867.
[24]
Ouali, A.; Spindler, J.F.; Jutand, A.; Taillefer, M. nitrogen ligands in copper-catalyzed arylation of phenols: Structure/activity relationships and applications. Adv. Synth. Catal., 2007, 349(11-12), 1906-1916.
[25]
Hosseinzadeh, R.; Tajbakhsh, M.; Alikarami, M. Copper-Catalyzed N-Arylation of diazoles with Aryl bromides using KF/Al2O3: An improved protocol. Tetrahedron Lett., 2006, 47(29), 5203-5205.
[26]
Xia, N.; Taillefer, M. Copper- or Iron-Catalyzed arylation of phenols from respectively Aryl chlorides and Aryl iodides. Chemistry. - Eur. J, 2008, 14(20), 6037-6039.
[27]
Kidwai, M.; Mishra, N.K.; Bansal, V.; Kumar, A.; Mozumdar, S. Cu-Nanoparticle catalyzed O-Arylation of phenols with Aryl halides via ullmann coupling. Tetrahedron Lett., 2007, 48(50), 8883-8887.
[28]
Miao, T.; Wang, L. Immobilization of copper in organic-inorganic hybrid materials: A highly efficient and reusable catalyst for the ullmann diaryl etherification. Tetrahedron Lett., 2007, 48, 95-99.
[29]
Benyahya, S.; Monnier, F.; Taillefer, M.; Man, M.W.C.; Bied, C.; Ouazzani, F. Efficient and versatile Sol-Gel immobilized copper catalyst for ullmann arylation of phenols. Adv. Synth. Catal., 2008, 350(14-15), 2205-2208.
[30]
Choudary, B.M.; Sridhar, C.; Kantam, M.L.; Venkanna, G.T.; Sreedhar, B. Design and evolution of copper apatite catalysts for N-Arylation of heterocycles with Chloro- and Fluoroarenes. J. Am. Chem. Soc., 2005, 127(28), 9948-9949.
[31]
Monnier, F.; Taillefer, M. Catalytic C-C, C-N, and C-O ullmann-type coupling reactions. Angewandte Chemie – Intl. Ed, 2009, 48(38), 6954-6971.
[32]
Sagar, A.D.; Tale, R.H.; Adude, R.N. Synthesis of symmetrical diaryl ethers from arylboronic acids mediated by Copper(II) acetate. Tetrahedron Lett., 2003, 44(37), 7061-7063.
[33]
Evans, D.A.; Katz, J.L.; West, T.R. Synthesis of diaryl ethers through the Copper-Promoted arylation of phenols with arylboronic acids. An expedient synthesis of thyroxine. Tetrahedron Lett., 1998, 39(19), 2937-2940.
[34]
Takise, R.; Isshiki, R.; Muto, K.; Itami, K.; Yamaguchi, J. Decarbonylative diaryl ether synthesis by Pd and Ni catalysis. J. Am. Chem. Soc., 2017, 139(9), 3340-3343.
[35]
Jalalian, N.; Ishikawa, E.E.; Silva, L.F.; Olofsson, B. Room Temperature, metal-free synthesis of diaryl ethers with use of diaryliodonium salts. Org. Lett., 2011, 13(6), 1552-1555.
[36]
Lindstedt, E.; Ghosh, R.; Olofsson, B. Metal-Free synthesis of Aryl Ethers in water. Org. Lett., 2013, 15(23), 6070-6073.
[37]
Li, F.; Wang, Q.; Ding, Z.; Tao, F. Microwave-Assisted synthesis of diaryl ethers without catalyst. Org. Lett., 2003, 5(12), 2169-2171.
[38]
Huang, L.Z.; Han, P.; Li, Y.Q.; Xu, Y.M.; Zhang, T.; Du, Z.T. A facile and efficient synthesis of diaryl amines or ethers under microwave irradiation at presence of KF/AL2O3 without solvent and their anti-fungal biological activities against six phytopathogens. Int. J. Mol. Sci., 2013, 14(9), 18850-18860.
[39]
Lee, H.J.; Duke, S.O. Protoporphyrinogen IX-Oxidizing activities involved in the mode of action of peroxidizing herbicides. J. Agric. Food Chem., 1994, 42(11), 2610-2618.
[40]
Matringe, M.; Camadro, J.M.; Labbe, P.; Scalla, R. Protoporphyrinogen oxidase as a molecular target for diphenyl ether herbicides. Biochem. J., 1989, 260, 231-235.
[41]
Jacobs, J.M.; Jacobs, N.J. Measurement of protoporphyrinogen oxidase activity. Curr. Protoc. Toxicol., 2001, 8, 85.
[42]
Theodoridis, G. Protoporphyrinogen-IX-Oxidase inhibitors. In: Modern Crop Protect; Comp, 2008; pp. 53-186.
[43]
Yu, H.; Yang, H.; Cui, D.; Lv, L.; Li, B. Synthesis and herbicidal activity of diphenyl ether derivatives containing unsaturated carboxylates. J. Agric. Food Chem., 2011, 59(21), 11718-11726.
[44]
Hao, G.F.; Tan, Y.; Yu, N.X.; Yang, G.F. Structure-Activity relationships of diphenyl-ether as protoporphyrinogen oxidase inhibitors: Insights from computational simulations. J. Comput. Aided Mol. Des., 2011, 25(3), 213-222.
[45]
Hao, G.F.; Zhu, X.L.; Ji, F.Q.; Zhang, L.; Yang, G.F.; Zhan, C.G. Understanding the mechanism of drug resistance due to a codon deletion in protoporphyrinogen oxidase through computational modeling. J. Phys. Chem. B, 2009, 113(14), 4865-4875.
[46]
Kochi, A. The global tuberculosis situation and the new control strategy of the world health organization. 1991. Bull. World Health Organ., 2001, 79(1), 71-75.
[48]
Rattan, A.; Kalia, A.; Ahmad, N. Multidrug-Resistant mycobacterium tuberculosis: Molecular perspectives. Emerg. Infect. Dis., 1998, 4(2), 195-209.
[49]
Bloom, B.R.; Murray, C.J. Tuberculosis: Commentary on a reemergent killer. Science, 1992, 257(5073), 1055-1064.
[50]
Banerjee, A.; Dubnau, E.; Quemard, A.; Balasubramanian, V.; Um, K.; Wilson, T.; Collins, D.; de Lisle, G.; Jacobs, W. InhA, a Gene encoding a target for isoniazid and ethionamide in mycobacterium tuberculosis. Science(80-), 1994, 263(5144), 227-230.
[51]
Bertrand, T.; Eady, N.A.J.; Jones, J.N. Jesmin; Nagy, J.M.; Jamart-Grégoire, B.; Raven, E.L.; Brown, K.A. Crystal structure of mycobacterium tuberculosis catalase-peroxidase. J. Biol. Chem., 2004, 279(37), 38991-38999.
[52]
Ramaswamy, S.; Musser, J.M. Molecular genetic basis of antimicrobial agent resistance inmycobacterium tuberculosis: 1998 update. Tuber. Lung Dis., 1998, 79, 3-29.
[53]
Tonge, P.J.; Kisker, C.; Slayden, R.A. Development of modern InhA inhibitors to combat drug resistant strains of mycobacterium tuberculosis. Curr. Top. Med. Chem., 2007, 7(5), 489-498.
[54]
Sullivan, T.J.; Truglio, J.J.; Boyne, M.E.; Novichenok, P.; Zhang, X.; Stratton, C.F.; Li, H.J.; Kaur, T.; Amin, A.; Johnson, F. High affinity InhA inhibitors with activity against drug-resistant strains of mycobacterium tuberculosis. ACS Chem. Biol., 2006, 1, 43-53.
[55]
Cinu, T.A.; Sidhartha, S.K.; Indira, B.; Varadaraj, B.G.; Vishnu, P.S.; Shenoy, G.G. Design, synthesis and evaluation of antitubercular activity of triclosan analogues. Arab. J. Chem., 2015.
[http://dx.doi.org/10.1016/j.arabjc.2015.09.003]
[http://dx.doi.org/10.1016/j.arabjc.2015.09.003]
[56]
Luckner, S.R.; Liu, N.; Am Ende, C.W.; Tonge, P.J.; Kisker, C. A slow, tight binding inhibitor of InhA, the Enoyl-Acyl carrier protein reductase from mycobacterium tuberculosis. J. Biol. Chem., 2010, 285(19), 14330-14337.
[57]
Kini, S.G.; Bhat, A.R.; Bryant, B.; Williamson, J.S.; Dayan, F.E. Synthesis, antitubercular activity and docking study of novel cyclic azole substituted diphenyl ether derivatives. Eur. J. Med. Chem., 2009, 44(2), 492-500.
[58]
Cihlar, T.; Ray, A.S. Nucleoside and nucleotide HIV Reverse transcriptase inhibitors: 25 years after zidovudine. Antiviral Res., 2010, 85, 39-58.
[59]
Azijn, H.; Tirry, I.; Vingerhoets, J.; De Béthune, M.P.; Kraus, G.; Boven, K.; Jochmans, D.; Van Craenenbroeck, E.; Picchio, G.; Rimsky, L.T. TMC278, a next-Generation Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), active against Wild-Type and NNRTI-Resistant HIV-1. Antimicrob. Agents Chemother., 2010, 54(2), 718-727.
[60]
Mordant, C.; Schmitt, B.; Pasquier, E.; Demestre, C.; Queguiner, L.; Masungi, C.; Peeters, A.; Smeulders, L.; Bettens, E.; Hertogs, K. Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 Wild-Type and mutant strains. Eur. J. Med. Chem., 2007, 42(5), 567-579.
[61]
Tucker, T.J.; Saggar, S.; Sisko, J.T.; Tynebor, R.M.; Williams, T.M.; Felock, P.J.; Flynn, J.A.; Lai, M.T.; Liang, Y.; McGaughey, G. The design and synthesis of diaryl ether second generation HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) with enhanced potency versus key clinical mutations. Bioorg. Med. Chem. Lett., 2008, 18(9), 2959-2966.
[62]
Feng, X.Q.; Liang, Y.H.; Zeng, Z.S.; Chen, F.E.; Balzarini, J.; Pannecouque, C.; De Clercq, E. Structural modifications of DAPY analogues with potent Anti-HIV-1 activity. ChemMedChem, 2009, 4(2), 219-224.
[63]
Ferris, R.G.; Hazen, R.J.; Roberts, G.B.; St. Clair, M.H.; Chan, J.H.; Romines, K.R.; Freeman, G.A.; Tidwell, J.H.; Schaller, L.T.; Cowan, J.R. Antiviral activity of gw678248, a novel benzophenone nonnucleoside reverse transcriptase inhibitor. Antimicrob. Agents Chemother., 2005, 49(10), 4046-4051.
[64]
Meng, G.; Chen, F.E.; De Clercq, E.; Balzarini, J.; Pannecouque, C. Nonnucleoside HIV-1 reverse transcriptase inhibitors: Part i. synthesis and structure-activity relationship of 1-alkoxymethyl-5-alkyl-6-naphthylmethyl uracils as HEPT analogues. Chem. Pharm. Bull. , 2003, 51(7), 779-789.
[65]
Ma, X.D.; Zhang, X.; Dai, H.F.; Yang, S.Q.; Yang, L.M.; Gu, S.X.; Zheng, Y.T.; He, Q.Q.; Chen, F.E. Synthesis and Biological Activity of Naphthyl-Substituted (B-Ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg. Med. Chem., 2011, 19(15), 4601-4607.
[66]
Liang, Y-H.; Feng, X-Q.; Zeng, Z-S.; Chen, F-E.; Balzarini, J.; Pannecouque, C.; De Clercq, E. Design, synthesis, and sar of naphthyl-substituted diarylpyrimidines as Non-Nucleoside inhibitors of HIV-1 reverse transcriptase. ChemMedChem, 2009, 4(9), 1537-1545.
[67]
Liang, Y.H.; Chen, F.E. ONIOM DFT/PM3 Calculations on the interaction between Dapivirine and HIV-1 reverse transcriptase, a theoretical study. Drug Discov. Ther., 2007, 1, 57-60.
[68]
Kennedy-Smith, J.J.; Arora, N.; Billedeau, J.R.; Fretland, J.; Hang, J.Q.; Heilek, G.M.; Harris, S.F.; Hirschfeld, D.; Javanbakht, H.; Li, Y. Synthesis and biological activity of new pyridone diaryl ether non-nucleoside inhibitors of HIV-1 reverse transcriptase. MedChemComm, 2010, 1, 79-83.
[69]
Tucker, T.J.; Sisko, J.T.; Tynebor, R.M.; Williams, T.M.; Felock, P.J.; Flynn, J.A.; Lai, M.T.; Liang, Y.; McGaughey, G.; Liu, M. Discovery of 3-5-[(6-Amino-1H-Pyrazolo[3,4-b]Pyridine-3-Yl)Methoxy]-2-Chlorophenoxy-5-Chlorobenzonitrile (MK-4965): A potent, orally bioavailable HIV-1 non-nucleoside reverse transcriptase inhibitor with improved potency against key mutant viruses. J. Med. Chem., 2008, 51(20), 6503-6511.
[70]
Côté, B.; Burch, J.D.; Asante-Appiah, E.; Bayly, C.; Bédard, L.; Blouin, M.; Campeau, L.C.; Cauchon, E.; Chan, M.; Chefson, A. Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses. Bioorg. Med. Chem. Lett., 2014, 24(3), 917-922.
[71]
Gauthier, D.R.; Sherry, B.D.; Cao, Y.; Journet, M.; Humphrey, G.; Itoh, T.; Mangion, I.; Tschaen, D.M. Highly efficient synthesis of HIV NNRTI doravirine. Org. Lett., 2015, 17(6), 1353-1356.
[72]
David, C. Atkinson, Keith E. Godfrey, Bernard Meek, John F. Saville, and M. R. S. Substituted (2-Phenoxypheny1)acetic acids with antiinflammatory activity. J. Med. Chem., 1983, 26(10), 1353-1360.
[73]
Atkinson, D.C. A Comparison of the systemic anti-inflammatory activity of three different irritants in the rat. Arch. Int. Pharmacodyn. Ther., 1971, 193(2), 391-396.
[74]
Leach, D.C.A. and E.C. Anti-Inflammatory and related properties
of 2-(2, 4-dichlorophenoxy) phenylacetic acid (Fenclofenac)
CH2COOH. Agents Actions, 1976, 6, 657-666.
[75]
Han, Z.; Mei, W.; Zhao, Y.; Deng, Y.; Dai, H. A new cytotoxic isocoumarin from endophytic fungus Penicillium SP. 091402 of the mangrove plant bruguiera sexangula. Chem. Nat. Compd., 2009, 45(6), 805-807.
[76]
Sun, Z.L.; Zhang, M.; Zhang, J.F.; Feng, J. Antifungal and cytotoxic activities of the secondary metabolites from endophytic Fungus Massrison Sp. Phytomedicine, 2011, 18(10), 859-862.
[77]
Peng, W.; You, F.; Li, X.L.; Jia, M.; Zheng, C.J.; Han, T.; Qin, L.P. A new diphenyl ether from the endophytic fungus Verticillium sp. isolated from rehmannia glutinosa. Chin. J. Nat. Med., 2013, 11(6), 673-675.
[78]
Wang, F.W.; Ye, Y.H.; Chen, J.R.; Wang, X.T.; Zhu, H.L.; Song, Y.C.; Tan, R.X. Neoplaether, a new cytotoxic and antifungal endophyte metabolite from neoplaconema napellum IFB-E016. FEMS Microbiol. Lett., 2006, 261(2), 218-223.
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