Strategies for the Synthesis of Mono- and Bis-Thionaphthoquinones

Alcione    S.    de Carvalho; David    R.    da Rocha; Vitor    F.    Ferreira
Abstract

The subclass of compounds that have the nucleus 1, 4-naphthoquinone is the most diverse class of quinones, which have a large number of substances and have useful applications ranging from medicinal chemistry to application in materials with special properties. The introduction of one or two substituents with the sulfur heteroatom in the naphthoquinone nucleus generates products containing alkyl and aryl groups that amplify certain biological properties against bacteria, viruses, and fungi. There are several methods of preparing these compounds, mainly from low molecular weight naphthoquinones with two electrophilic sites capable of reacting with sulfides generating diversity and new classes of compounds, including new sulfur heterocycles and sulfur heterocycles fused with naphthoquinones. These compounds have been shown to be bioactive against several biological targets. This review will describe the methods of their synthesis and, when applicable, their biological activities.
Keywords: 1, 4-naphthoquinone, thionaphthoquinone, bis-thionaphthoquinone, sulfur-heterocycles, synthesis, medicinal chemistry.
Graphical Abstract

[1] 
Powis, G. Metabolism and reactions of quinoid anticancer agents. Pharmacol. Ther.,  1987, 35(1-2), 57-162.
[http://dx.doi.org/10.1016/0163-7258(87)90105-7] [PMID: 3321102] 
[2] 
Al-Snafi, A.E. Review on Lawsonia inermis, potential medicinal plant. Int. J. Curr. Pharm. Res.,  2019, 11, 1-13.
[3] 
Ahmad, T.; Suzuki, Y.J. Juglone in oxidative stress and cell signaling. Antioxidants,  2019, 8(4), 91.
[http://dx.doi.org/10.3390/antiox8040091] [PMID: 30959841] 
[4] 
Fowler, P.; Meurer, K.; Honarvar, N.; Kirkland, D. A review of the genotoxic potential of 1,4-naphthoquinone. Mutat. Res. Genet. Toxicol. Environ. Mutagen.,  2018, 834, 6-17.
[http://dx.doi.org/10.1016/j.mrgentox.2018.07.004] [PMID: 30173865] 
[5] 
Singh, D.K.; Luqman, S.; Mathur, A.K. Lawsonia inermis L. - A commercially important primaeval dying and medicinal plant with diverse pharmacological activity: A review. Ind. Crops Prod.,  2015, 65, 269-286.
[http://dx.doi.org/10.1016/j.indcrop.2014.11.025] 
[6] 
Portilho, A. J. S.; Gomes, C. B. S. M. R.; Nunes, C. F. A. M.; Moreira, C. S.; Rocha, D. D.; Rodrigues, D. R.; Mesquita, F. P.; Forezi, L. S. M.; Odorico, M. M. F.; Amaral, M. E. M.; Cordeiro, P. S.; Montenegro, R. C.; Do Nascimento, V.; Ferreira, V. F.  Use of thioethers derived from intermediate 2-
	chlorojuglone as potential antitumor agents and modulators of leukemia
	chemoresistance. PI BR 102018007385 A2 20191029, , 2019.
[7] 
Ferreira, V. F.; Jordao, A. K.; Novais, J. S.; de Almeida, H. C. C. C.  Preparation
	of naphthoquinones as antimicrobial agents, and their compostions and
	use in diagnostic kits. PI BR 102013026761 A2 20150728,, 2015.
[8] 
Santos, W. C.; Ferreira, V. F.; Baptista, F. S.; Da Rocha, D. R. Preparation of
	lapachol and related 3-alkyl-2-hydroxy-1,4-naphthoquinones. PI BR
	2010003106 A2 20121211,, 2012.
[9] 
Jordão, A.K.; Vargas, M.D.; Pinto, A.C.; da Silva, F.C.; Ferreira, V.F. Lawsone in organic synthesis. RSC Adv,  2015, 5, 67909-67943.
[http://dx.doi.org/10.1039/C5RA12785H] 
[10] 
Chaudhary, A.; Khurana, J.M. 2-hydroxy-1,4-naphthoquinone: A versatile synthon in organic synthesis. Curr. Org. Chem.,  2016, 20, 1314-1344.
[http://dx.doi.org/10.2174/1385272820666151125231522] 
[11] 
Ribeiro, R.C.B.; de Freitas, P.P.; Moreira, C.S.; de Moraes, L.G.C.; de Moraes, M.G.; da Silva, F.C.; Rocha, D.R.; Gimba, E.R.P.; Ferreira, V.F. A new strategy for the synthesis of nonsymmetrical 3,3′-(Aryl/alkyl- methylene) bis-2-hydroxy-1,4-naphthoquinones and their cytotoxic effects in pc3 prostate cancer cells. J. Braz. Chem. Soc.,  2020, 31, 288-297.
[http://dx.doi.org/10.21577/0103-5053.20190172] 
[12] 
Badave, K.D.; Khan, A.A.; Rane, S.Y. Anticancer vitamin K3 analogues: A review. Anticancer. Agents Med. Chem.,  2016, 16(8), 1017-1030.
[http://dx.doi.org/10.2174/1871520616666160310143316] [PMID: 26961313] 
[13] 
Endale, M.; Erdelyi, M. Recent trends in heterocyclic quinones. Targ. Heterocyc. Sys.,  2012, 16, 184-220.
[14] 
Acton, E.M.; Tong, G.L.; Mosher, C.W.; Smith, T.H.; Henry, D.W. 7-(Aminoethyl) ether and thioether of daunomycinone. J. Med. Chem.,  1979, 22(8), 922-926.
[http://dx.doi.org/10.1021/jm00194a007] [PMID: 490537] 
[15] 
Kurylowicz, W. Antibióticos: Uma revisão Crítica; UFPE: Recife, 1981. 
[16] 
Jaya, P.S.; Subedi, Y.P.; Chen, L.; Chang, C.W.T. A mode of action study of cationic anthraquinone analogs: A new class of highly potent anticancer agents. MedChemComm,  2015, 6, 2012-2023.
[http://dx.doi.org/10.1039/C5MD00314H] 
[17] 
Wilhanson, J.; Scott-Finningan, T.J. Trypanocidal activity of daunorubicin and related compounds. Nature,  1981, 292, 466-467.
[18] 
Subramanian, S.; Ferreira, M.M.C.; Trsic, M. A structure-activity relationship study of lapachol and some derivatives of 1, 4-naphthoquinones against carcinosarcoma Walker 256. Struct. Chem.,  1998, 9, 47-52.
[http://dx.doi.org/10.1023/A:1022487632133] 
[19] 
Rao, K.V.; Mcbride, T.J.; Oleson, J.J. Recognition and evaluation of lapachol as an antitumor agent. Cancer Res.,  1968, 28, 1952-1954.
[20] 
Gibbs, R.D. Chemotaxonomy of Flowering Plants; University Press: Montreal, 1974. 
[http://dx.doi.org/10.2307/j.ctt1w0ddx8] 
[21] 
Arnaudon, M. Hebdomadaires des Séances de l’Académie des Sciences. CR (East Lansing Mich.),  1858, 46, 1152-1156.
[22] 
Ferreira, V.F. Aprendendo sobre os conceitos de ácidos e bases. Quim. Nova na Escola,  1996, 4, 35-36.
[23] 
Barbosa, T.P.; Neto, H.D. Preparação de derivados do lapachol em meio ácido e em meio básico: uma proposta de experimentos para a disciplina de Química Orgânica Experimental. Quim. Nova,  2013, 36, 331-334.
[http://dx.doi.org/10.1590/S0100-40422013000200021] 
[24] 
Weaver, R.J.; Dickins, M.; Burke, M.D. Cytochrome P450 2C9 is responsible for hydroxylation of the naphthoquinone antimalarial drug 58C80 in human liver. Biochem. Pharmacol.,  1993, 46(7), 1183-1197.
[http://dx.doi.org/10.1016/0006-2952(93)90467-B] [PMID: 8216369] 
[25] 
Canfield, C.J.; Pudney, M.; Gutteridge, W.E. Interaction of atovaquone antimalarial drugs against Plasmodium falciparum in vitro. Exp. Parasitol.,  1995, 80, 373-381.
[26] 
Olliaro, P.; Wirth, P.D. New targets for antimalarial drug discovery. J. Pharm. Pharmacol.,  1997, 49, 29-33.
[27] 
Ball, M.D.; Bartlett, M.S.; Shaw, M.; Smith, J.W.; Nasr, M.; Meshnick, S.R. Activities and conformational fitting of 1,4-naphthoquinone derivatives and other cyclic 1,4-diones tested in vitro against Pneumocystis carinii. Antimicrob. Agents Chemother.,  2001, 45(5), 1473-1479.
[http://dx.doi.org/10.1128/AAC.45.5.1473-1479.2001] [PMID: 11302813] 
[28] 
Färnert, A.; Lindberg, J.; Gil, P.; Swedberg, G.; Berqvist, Y.; Thapar, M.M.; Lindegårdh, N.; Berezcky, S.; Björkman, A. Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: Case reports. BMJ,  2003, 326(7390), 628-629.
[http://dx.doi.org/10.1136/bmj.326.7390.628] [PMID: 12649236] 
[29] 
Hashemi-Fesharki, R. Chemotherapeutic value of parvaquone and buparvaquone against Theileria annulata infection of cattle. Res. Vet. Sci.,  1991, 50(2), 204-207.
[http://dx.doi.org/10.1016/0034-5288(91)90107-Y] [PMID: 2034901] 
[30] 
da Silva, F.C.; Ferreira, V.F. Natural naphthoquinones with great importance in medicinal chemistry. Curr. Org. Synth.,  2016, 13, 334-371.
[http://dx.doi.org/10.2174/1570179412666150817220343] 
[31] 
Colucci, M.A.; Moody, C.J.; Couch, G.D. Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: From synthetic organic chemistry to compounds with anticancer potential. Org. Biomol. Chem.,  2008, 6(4), 637-656.
[http://dx.doi.org/10.1039/B715270A] [PMID: 18264564] 
[32] 
Rau, G.; Cretu, F.M.; Andrei, A.M.; Pisoschi, C.G.; Mogosanu, G.D.; Boroghina, A.; Banita, I.M.; Stanciulescu, C.E. Synthesis and evaluation of antimicrobial activity of new 2-mercapto-3-substituted-1,4-naphthoquinones. Farmacia,  2015, 63, 665-669.
[33] 
Delarmelina, M.; Dalto, R.D.; Cerri, M.F.; Madeira, K.P.; Rangel, L.B.A.; Junior, V.L.; Romao, W.; Tarantod, A.G.; Greco, S.J. Synthesis, antitumor activity and docking of 2,3-(substituted)-1,4-naphthoquinone derivatives containing nitrogen, oxygen and sulfur. J. Braz. Chem. Soc.,  2015, 26, 1804-1816.
[http://dx.doi.org/10.5935/0103-5053.20150157] 
[34] 
Zakharova, O.A.; Goryunov, L.I.; Troshkova, N.M.; Ovchinnikova, L.P.; Shteingarts, V.D.; Nevinsky, G.A. Cytotoxicity of new n-butylamino and sulfur-containing derivatives of polyfluorinated 1,4-naphthoquinone. Eur. J. Med. Chem.,  2010, 45(1), 270-274.
[http://dx.doi.org/10.1016/j.ejmech.2009.10.006] [PMID: 19883955] 
[35] 
Huang, G.; Dong, J.Y.; Zhang, Q.J.; Meng, Q.Q.; Zhao, H.R.; Zhu, B.Q.; Li, S.S. Discovery and synthesis of sulfur-containing 6-substituted 5,8-dimethoxy-1,4-naphthoquinone oxime derivatives as new and potential anti-MDR cancer agents. Eur. J. Med. Chem.,  2019, 165, 160-171.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.005] [PMID: 30677614] 
[36] 
Nutter, L.M.; Cheng, A.L.; Hung, H.L.; Hsieh, R.K.; Ngo, E.O.; Liu, T.W. Menadione: spectrum of anticancer activity and effects on nucleotide metabolism in human neoplastic cell lines. Biochem. Pharmacol.,  1991, 41(9), 1283-1292.
[http://dx.doi.org/10.1016/0006-2952(91)90099-Q] [PMID: 2018560] 
[37] 
Tamura, K.; Southwick, E.C.; Kerns, J.; Rosi, K.; Carr, B.I.; Wilcox, C.; Lazo, J.S. Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue. Cancer Res.,  2000, 60(5), 1317-1325.
[PMID: 10728693] 
[38] 
Nutter, L.M.; Ngo, E.O.; Fisher, G.R.; Gutierrez, P.L. DNA strand scission and free radical production in menadione-treated cells. Correlation with cytotoxicity and role of NADPH quinone acceptor oxidoreductase. J. Biol. Chem.,  1992, 267(4), 2474-2479.
[http://dx.doi.org/10.1016/S0021-9258(18)45903-0] [PMID: 1370822] 
[39] 
Nishikawa, Y.; Carr, B.I.; Wang, M.; Kar, S.; Finn, F.; Dowd, P.; Zheng, Z.B.; Kerns, J.; Naganathan, S. Growth inhibition of hepatoma cells induced by vitamin K and its analogs. J. Biol. Chem.,  1995, 270(47), 28304-28310.
[http://dx.doi.org/10.1074/jbc.270.47.28304] [PMID: 7499329] 
[40] 
Wang, Z.; Southwick, E.C.; Wang, M.; Kar, S.; Rosi, K.S.; Wilcox, C.S.; Lazo, J.S.; Carr, B.I. Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition induced by novel K vitamin analogs. Cancer Res.,  2001, 61(19), 7211-7216.
[PMID: 11585757] 
[41] 
Wang, Z.; Wang, M.; Carr, B.I. Hepatocyte growth factor enhances protein phosphatase Cdc25A inhibitor compound 5-induced hepatoma cell growth inhibition via Akt-mediated MAPK pathway. J. Cell. Physiol.,  2005, 203(3), 510-519.
[http://dx.doi.org/10.1002/jcp.20243] [PMID: 15534860] 
[42] 
Han, Y.; Shen, H.; Carr, B.I.; Wipf, P.; Lazo, J.S.; Pan, S.S. NAD(P)H:Quinone oxidoreductase-1-dependent and -independent cytotoxicity of potent quinone Cdc25 phosphatase inhibitors. J. Pharmacol. Exp. Ther.,  2004, 309(1), 64-70.
[http://dx.doi.org/10.1124/jpet.103.059477] [PMID: 14718602] 
[43] 
Yang, Y.; Yang, W.S.; Yu, T.; Yi, Y.S.; Park, J.G.; Jeong, D.; Kim, J.H.; Oh, J.S.; Yoon, K.; Kim, J.H.; Cho, J.Y. Novel anti-inflammatory function of NSC95397 by the suppression of multiple kinases. Biochem. Pharmacol.,  2014, 88(2), 201-215.
[http://dx.doi.org/10.1016/j.bcp.2014.01.022] [PMID: 24468133] 
[44] 
Wellington, K.W.; Hlatshwayo, V.; Kolesnikova, N.I.; Saha, S.T.; Kaur, M.; Motadi, L.R. Anticancer activities of vitamin K3 analogues. Invest. New Drugs,  2020, 38(2), 378-391.
[http://dx.doi.org/10.1007/s10637-019-00855-8] [PMID: 31701430] 
[45] 
de Paiva, Y.G.; Silva, T.L.; Xavier, A.F.A.; Cardoso, M.F.C.; Silva, F.C.; Silva, M.F.S.; Pinheiro, D.P.; Pessoa, C.; Ferreira, V.F.; Goulart, M.O.F. Relationship between electrochemical parameters, cytotoxicity data against cancer cells of 3-thio-substituted nor-beta-lapachone derivatives. Implications for cancer therapy. J. Braz. Chem. Soc.,  2019, 30, 658-672.
[http://dx.doi.org/10.21577/0103-5053.20180248] 
[46] 
Jardim, G.A.M.; Oliveira, W.X.C.; de Freitas, R.P.; Menna-Barreto, R.F.S.; Silva, T.L.; Goulart, M.O.F.; da Silva Júnior, E.N. Direct sequential C-H iodination/organoyl-thiolation for the benzenoid A-ring modification of quinonoid deactivated systems: A new protocol for potent trypanocidal quinones. Org. Biomol. Chem.,  2018, 16(10), 1686-1691.
[http://dx.doi.org/10.1039/C8OB00196K] [PMID: 29450434] 
[47] 
Bayrak, N.; Yildirim, H.; Tuyun, A.F.; Kara, E.M.; Celik, B.O.; Gupta, G.K. Synthesis, biological, and computational study of naphthoquinone derivatives containing heteroatoms. J. Chem. Soc. Pak.,  2016, 38, 1211-1221.
[48] 
Tandon, V.K.; Singh, R.V.; Yadav, D.B. Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents. Bioorg. Med. Chem. Lett.,  2004, 14(11), 2901-2904.
[http://dx.doi.org/10.1016/j.bmcl.2004.03.047] [PMID: 15125956] 
[49] 
Sreelatha, T.; Kandhasamy, S.; Dinesh, R.; Shruthy, S.; Shweta, S.; Mukesh, D.; Karunagaran, D.; Balaji, R.; Mathivanan, N.; Perumal, P.T. Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives. Bioorg. Med. Chem. Lett.,  2014, 24(15), 3647-3651.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.080] [PMID: 24913712] 
[50] 
Nishikawa, Y.; Wang, Z.; Kerns, J.; Wilcox, C.S.; Carr, B.I. Inhibition of hepatoma cell growth in vitro by arylating and non-arylating K vitamin analogs. Significance of protein tyrosine phosphatase inhibition. J. Biol. Chem.,  1999, 274(49), 34803-34810.
[http://dx.doi.org/10.1074/jbc.274.49.34803] [PMID: 10574951] 
[51] 
Krishna, T.P.A.; Pandaram, S.; Chinnasamy, S.; Ilangovan, A. Oxidative radical coupling of hydroquinones and thiols using chromic acid: One-pot synthesis of quinonyl alkyl/aryl thioethers. RSC Advances,  2020, 10, 19454-19462.
[http://dx.doi.org/10.1039/D0RA01519A] 
[52] 
Ryu, C.K.; Choi, K.U.; Shim, J.Y.; You, H.J.; Choi, I.H.; Chae, M.J. Synthesis and antifungal activity of 6-arylthio-/6-arylamino-4,7-dioxobenzothiazoles. Bioorg. Med. Chem.,  2003, 11(18), 4003-4008.
[http://dx.doi.org/10.1016/S0968-0896(03)00390-0] [PMID: 12927862] 
[53] 
Jali, B.R.; Kuang, Y.; Neamati, N.; Baruah, J.B. Selective binding of naphthoquinone derivatives to serum albumin proteins and their effects on cytotoxicity. Chem. Biol. Interact.,  2014, 214, 10-17.
[http://dx.doi.org/10.1016/j.cbi.2014.01.014] [PMID: 24560625] 
[54] 
Cole, W.C.; Wolf, W. Preparation and metabolism of a cisplatin/serum protein complex. Chem. Biol. Interact.,  1980, 30(2), 223-235.
[http://dx.doi.org/10.1016/0009-2797(80)90128-3] [PMID: 7190078] 
[55] 
Wexselblatt, E.; Gibson, D. What do we know about the reduction of Pt(IV) pro-drugs? J. Inorg. Biochem.,  2012, 117, 220-229.
[http://dx.doi.org/10.1016/j.jinorgbio.2012.06.013] [PMID: 22877926] 
[56] 
Zhang, J.Z.; Wexselblatt, E.; Hambley, T.W.; Gibson, D. Pt(IV) analogs of oxaliplatin that do not follow the expected correlation between electrochemical reduction potential and rate of reduction by ascorbate. Chem. Commun. (Camb.),  2012, 48(6), 847-849.
[http://dx.doi.org/10.1039/C1CC16647F] [PMID: 22124352] 
[57] 
Fries, K.; Ochwaltt, P. Neuee aber Dichlor-2.8-naphthochinon-1.4. Chem. Ber.,  1923, 56, 1291-1304.
[http://dx.doi.org/10.1002/cber.19230560609] 
[58] 
Oediger, H.; Joop, N. p-Chinone mit Mercaptoacetamid-Gruppierungen. Liebigs Ann. Chem.,  1972, 758, 1-12.
[http://dx.doi.org/10.1002/jlac.19727580102] 
[59] 
Stasevych, M.V.; Plotnikov, M.P.; Platonov, M.O.; Sabat, S.I.; Musyanovych, R.Y.; Novikov, V.P. Sulfur-Containing Derivatives of 1,4-Naphthoquinone, Part 1: Disulfide Synthesis. Heteroatom Chem.,  2005, 16, 205-211.
[http://dx.doi.org/10.1002/hc.20112] 
[60] 
Moscow, K. Synthesis of Organic Preparations, 1960.
[61] 
Kofod, H. 2-furfuryl mercaptan. Org Synth Coll,  1963, 4, 491-493.
[62] 
Tandon, V.K.; Maurya, H.K.; Mishra, N.N.; Shukla, P.K. Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents. Eur. J. Med. Chem.,  2009, 44(8), 3130-3137.
[http://dx.doi.org/10.1016/j.ejmech.2009.03.006] [PMID: 19349095] 
[63] 
Tandon, V.K.; Maurya, H.K. Facile and efficient synthesis of 1,4-benzodiazepines from 1,4-naphthoquinones. Heterocycles,  2008, 76, 1007-1010.
[http://dx.doi.org/10.3987/COM-08-S(N)63] 
[64] 
Wang, X.L.; Zheng, X.F.; Wang, L.; Reiner, J.; Xie, W.L.; Chang, J.B. [1,1′ Bis-(diphenylphosphino)-ferrocene]-dichloropalladium/1,1′-Bis-(diphenylphosphino) ferrocene catalyzed synthesis of 2,3-diamino-1,4-naphthoquinones. Synthesis,  2007, 7, 989-998.
[65] 
Ibis, C.; Tuyun, A.F.; Bahar, H.; Ayla, S.S.; Stasevych, M.V.; Musyanovych, R.Y.; Komarovska-Porokhnyavets, O.; Novikov, V. Nucleophilic substitution reactions of 1,4-naphthoquinone and biologic properties of novel S-, S,S-, N-, and N,S-substituted 1,4-naphthoquinone derivatives. Med. Chem. Res.,  2014, 23, 2140-2149.
[http://dx.doi.org/10.1007/s00044-013-0806-y] 
[66] 
Tandon, V.K.; Maurya, H.K.; Kumar, S.; Rashid, A.; Panda, D. Synthesis and evaluation of 2-heteroaryl and 2,3-diheteroaryl-1,4-naphthoquinones that potently induce apoptosis in cancer cells. RSC Advances,  2014, 4, 12441-12447.
[http://dx.doi.org/10.1039/C3RA47720G] 
[67] 
Niculescu, V.C.; Muresan, N.; Salageanu, A.; Tucureanu, C.; Marinescu, G.; Chirigiu, L.; Lepadatu, C. Novel 2,3-disubstituted-1,4-naphthoquinone derivatives and their metal complexes e synthesis and in vitro cytotoxic effect against mouse fibrosarcoma L929 cells. J. Organomet. Chem.,  2012, 700, 13-19.
[http://dx.doi.org/10.1016/j.jorganchem.2011.10.036] 
[68] 
Huang, S.T.; Kuo, H.S.; Hsiao, C.L.; Lin, Y.L. Efficient synthesis of ‘redox-switched’ naphthoquinone thiol-crown ethers and their biological activity evaluation. Bioorg. Med. Chem.,  2002, 10(6), 1947-1952.
[http://dx.doi.org/10.1016/S0968-0896(02)00004-4] [PMID: 11937353] 
[69] 
Ibis, C.; Tuyun, A.F.; Ozsoy-Gunes, Z.; Bahar, H.; Stasevych, M.V.; Musyanovych, R.Y.; Komarovska-Porokhnyavets, O.; Novikov, V. Synthesis and biological evaluation of novel nitrogen- and sulfur-containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents. Eur. J. Med. Chem.,  2011, 46(12), 5861-5867.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.048] [PMID: 22019185] 
[70] 
Ibis, C.; Tuyun, A.F.; Bahar, H.; Ayla, S.S.; Stasevych, M.V.; Musyanovych, R.Y.; Komarovska-Porokhnyavets, O.; Novikov, V. Synthesis of novel 1,4-naphthoquinone derivatives: antibacterial and antifungal agents. Med. Chem. Res.,  2013, 22, 2879-2888.
[http://dx.doi.org/10.1007/s00044-012-0300-y] 
[71] 
Ibis, C.; Ayla, S.S.; Asar, H. Synthesis and spectral and electrochemical characterization of novel substituted 1,4-Naphthoquinone derivatives. Synth. Commun.,  2014, 44, 121-126.
[http://dx.doi.org/10.1080/00397911.2013.793774] 
[72] 
Tandon, V.K.; Maurya, H.K.; Yadav, D.B.; Tripathi, A.; Kumar, M.; Shukla, P.K. Naphtho[2,3-b][1,4]-thiazine-5,10-diones and 3-substituted-1,4-dioxo-1,4-dihydronaphthalen-2-yl-thioalkanoate derivatives: synthesis and biological evaluation as potential antibacterial and antifungal agents. Bioorg. Med. Chem. Lett.,  2006, 16(22), 5883-5887.
[http://dx.doi.org/10.1016/j.bmcl.2006.08.060] [PMID: 16949283] 
[73] 
Thomson, R.H.; Worthington, R.D. Quinones. Part 9. Side-chain alkylthiolation of methyl-1,4-naphthoquinones. J. Chem. Soc., Perkin Trans. 1,  1980, 282-288.
[http://dx.doi.org/10.1039/p19800000282] 
[74] 
Thomson, R.H.; Worthington, R.D. Quinones. Part 10. Side-chain alkylthiolation of methyl-1,4-naphthoquinones. J. Chem. Soc., Perkin Trans. 1,  1980, 289-292.
[http://dx.doi.org/10.1039/p19800000289] 
[75] 
Sharma, A.; Santos, I.O.; Gaur, P.; Ferreira, V.F.; Garcia, C.R.S.; da Rocha, D.R. Addition of thiols to o-quinone methide: new 2-hydroxy-3-phenylsulfanylmethyl[1,4]naphthoquinones and their activity against the human malaria parasite Plasmodium falciparum (3D7). Eur. J. Med. Chem.,  2013, 59, 48-53.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.052] [PMID: 23202850] 
[76] 
Pinto, E.G.; Santos, I.O.; Schmidt, T.J.; Borborema, S.E.; Ferreira, V.F.; Rocha, D.R.; Tempone, A.G. Potential of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against Leishmania (L.) infantum: biological activity and structure-activity relationships. PLoS One,  2014, 9(8)e105127
[http://dx.doi.org/10.1371/journal.pone.0105127] [PMID: 25171058] 
[77] 
Lara, L.S.; Moreira, C.S.; Calvet, C.M.; Lechuga, G.C.; Souza, R.S.; Bourguignon, S.C.; Ferreira, V.F.; Rocha, D.; Pereira, M.C.S. Efficacy of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinone derivatives against different Trypanosoma cruzi discrete type units: Identification of a promising hit compound. Eur. J. Med. Chem.,  2018, 144, 572-581.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.052] [PMID: 29289882] 
Cite As
Current Organic Synthesis

Strategies for the Synthesis of Mono- and Bis-Thionaphthoquinones

Abstract

Graphical Abstract
