The Diversity of Heterocyclic N-oxide Molecules: Highlights on their Potential in Organic Synthesis, Catalysis and Drug Applications

Author(s): Dongli Li, Panpan Wu, Ning Sun, Yu-Jing Lu, Wing-Leung Wong*, Zhiyuang Fang*, Kun Zhang*.

Journal Name: Current Organic Chemistry

Volume 23 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The synthesis and chemistry of heterocyclic N-oxide derivatives such as those from pyridine and indazole are very well-known due to their usefulness as versatile synthetic intermediates and their biological importance. These classes of organic compounds have been demonstrated in many interesting and amazing functionalities, particularly vital in the areas including metal complexes formation, catalysts design, asymmetric catalysis and synthesis, and medicinal applications (some potent N-oxide compounds with anticancer, antibacterial, anti-inflammatory activity, etc.). Therefore, the heterocyclic N-oxide motif has been successfully employed in a number of recent advanced chemistry and drug development investigations. In the present review, our primary aim was to provide a relevant summary focusing on the topics of organic synthesis and medical application potential of the compounds cited, which could be attractive and give some insights to researchers in the field. Therefore, we mainly highlight the importance of heterocyclic N-oxide derivatives including those synthesized from imidazole, indazole, indole, pyridazine, pyrazine, pyridine, and pyrimidine in organic syntheses and catalysis, and drug applications. Over the past years, a number of reviews have been published on the organic synthesis and catalysis of N-oxides. We thus concentrated on highlighting those rarely mentioned or recently reported systems.

Keywords: Heterocyclic N-oxide, chelating ligand, catalysis, bioactive compounds, structural diversity, molecular drug design, medicinal agents.

[1]
Albini, A. Synthetic utility of amine N-oxides. Synthesis, 1993, 1993(3), 263-277.
[2]
Youssif, S. Recent trends in the chemistry of pyridine N-oxides. ARKIVOC, 2001, 12(4), 348-355.
[3]
Quagliano, J.V.; Fujita, J.; Franz, G.; Phillips, D.J.; Walmsley, J.A.; Tyree, S.Y. The Donor Properties of Pyridine N-Oxide. J. Am. Chem. Soc., 1961, 83(18), 3770-3773.
[4]
Carlin, R.L.; O’Connor, C.J.; Bhatia, S.N. Magnetic investigation of the electronic structure of hexakis (pyridine N-oxide) cobalt(II) perchlorate. J. Am. Chem. Soc., 1976, 98(3), 685-688.
[5]
Luh, T-Y. Trimethylamine N-oxide—A versatile reagent for organometallic chemistry. Coord. Chem. Rev., 1984, 60, 255-276.
[6]
Katritzky, A.R.; Lagowski, J.M. N-oxides and related compounds. Part XVIII. Proton nuclear magnetic resonance spectra of 4-substituted pyridines and pyridine 1-oxides. J. Chem. Soc., 1961, 43-46.
[7]
Garvey, R.G.; Nelson, J.H.; Ragsdale, R.O. The coordination chemistry of aromatic amine N-oxides. Coord. Chem. Rev., 1968, 3(3), 375-407.
[8]
Orchin, M.; Schmidt, P.J. Pyridine n-oxide complexes of platinum(II). Coord. Chem. Rev., 1968, 3(3), 345-373.
[9]
Kubota, T. Molecular Complexes and Their Spectra. XVIII. Iodine Complexes with Tertiary Amine N-Oxides. J. Am. Chem. Soc., 1965, 87(3), 458-468.
[10]
Ross, S.D.; Kelly, D.J.; Labes, M.M. Molecular compounds. VII. Interactions between 1,3,5-Trinitrobenzene and Pyridine-N-Oxides in Chloroform Solution. J. Am. Chem. Soc., 1956, 78(15), 3625-3627.
[11]
Chelucci, G.; Murineddu, G.; Pinna, G.A. Chiral pyridine N-oxides: useful ligands for asymmetric catalysis. Tetrahedron Asymmetry, 2004, 15(10), 1373-1389.
[12]
Kocovsky, P.; Malkov, A.V. From transition metals to organocatalysis. Russ. Chem. Bull., 2004, 53(9), 1806-1812.
[13]
Chen, J.; Takenaka, N. Helical chiral Pyridine N-Oxides: A new family of asymmetric catalysts. Chemistry Eur. J.,, 2009, 15(30), 7268-7276.
[14]
Jia, J.; Hubberstey, P.; Champness, N.R.; Schroder, M. Supramolecular chemistry of 4,4′-bipyridine-N,N′-dioxide in transition metal complexes: A rich diversity of coordinate, hydrogen-bond and aromatic stacking interactions. Struct. Bonding, 2009, 132, 135-161.
[15]
Kishbaugh, T.L.S. Six-membered ring systems: pyridine and benzo derivatives. Progress in Heterocyclic Chem., 2012, 24, 343-391.
[16]
Yeom, H-S.; Shin, S. Catalytic access to a-Oxo gold carbenes by N-O bond oxidants. Acc. Chem. Res., 2014, 47(3), 966-977.
[17]
Liu, X.; Lin, L.; Feng, X.; Chiral, N. N′-dioxide ligands: synthesis, coordination chemistry and asymmetric catalysis. Org. Chem. Front., 2014, 1, 298-302.
[18]
Liu, N.; Shu, Y-J.; Wang, B-Z.; Li, X-Z.; Bi, F-Q. Cyclization: A useful approach for the synthesis of nitrogen heterocyclic N-oxides. Curr. Org. Chem., 2015, 19(19), 1896-1915.
[19]
Koukal, P. Ulč. J.; Nečas, D.; Kotora, M. Pyridine N-Oxides and derivatives thereof in organocatalysis; Heterocyclic N-Oxides, 2017, pp. 29-58.
[20]
Katritzky, A.R. The chemistry of the aromatic heterocyclic N-oxides. Q. Rev. Chem. Soc., 1956, 10, 395-406.
[21]
Abramovitch, R.A.; Grins, G.; Rogers, R.B.; Shinkai, I. Alkylation of pyridine 1-oxides and related compounds with activated acetylenes. A novel molecular rearrangement of heteroaromatic N-oxides. J. Am. Chem. Soc., 1976, 98(18), 5671-5677.
[22]
Vozza, J.F. Reactions of 2-Picoline 1-Oxide with Reactive Halides. J. Org. Chem., 1962, 27(11), 3856-3860.
[23]
Karayannis, N.M. Metal complexes of aromatic amine n-oxides. Coord. Chem. Rev., 1973, 11(2), 93-159.
[24]
Garvey, R.G.; Ragsdale, R.O. Co-ordination complexes of oxovanadium (IV) with substituted pyridine 1-oxides. Coord. Chem. Rev., 1967, 29(3), 745-754.
[25]
Lever, A.B.P.; Lewis, J.; Nyholm, R.S. Metal complexes of picolinic acid N-oxide. J. Chem. Soc., 1962, 5262-5270.
[26]
Simpson, P.G.; Vinciguerra, A.; Guagliano, J.V. The Donor Properties of 2,2′-Bipyridine N,N′-Dioxide. Inorg. Chem., 1963, 2(2), 282-286.
[27]
Sartorelli, U.; Canziani, F.; Zingales, F. Substituted halocarbonyl complexes of Rhenium(I) with ligands having oxygen as the donor atom. Inorg. Chem., 1966, 5(12), 2233-2236.
[28]
Reiff, W.M.; Baker, A. Transition metal complexes of 2,2′,2”-terpyridine 1,1′,1”-trioxide. Inorg. Chem., 1970, 9(3), 570-576.
[29]
Mirrison, M.M.; Sawyer, D.T. 2,2′-Bipyridine 1,1′-dioxide and 2,2′,2”-terpyridine 1,1′,1”-trioxide complexes of manganese(II), -(III), and -(IV). Inorg. Chem., 1978, 17(2), 338-339.
[30]
Thummel, R.P.; Lefoulon, F. Polyaza cavity shaped molecules. 2. Annelated derivatives of 2,2′-biquinoline and the corresponding N-oxides. J. Org. Chem., 1985, 50(5), 666-670.
[31]
Ito, K.; Nagata, T.; Tanaka, K. Synthesis and electrochemical properties of transition metal complexes of 2,2′:6′,2”-terpyridine 1,1”-dioxide. Inorg. Chem., 2001, 40(24), 6331-6333.
[32]
Amoroso, A.J.; Burrows, M.W.; Dickinson, A.A.; Jones, C.; Willock, D.J.; Wong, W-T. Geometrical preferences of complexes of terpyridine N-oxide ligands: synthesis and crystal structures of nickel(II) with terpyridine 1,1′,1″-trioxide, terpyridine 1,1″-dioxide and terpyridine 1-oxide. J. Chem. Soc., Dalton Trans., 2001, 0, 225-227.
[33]
Fallahpour, R.A.; Neuburger, M. An efficient, easy route for the synthesis of 2,2′:6′,2′′‐terpyridine 1′‐oxides. Eur. J. Org. Chem., 2001, 1853-1856.
[34]
Musumeci, A.; Bonomo, R.P.; Cucinotta, V.; Seminara, A. Lanthanide complexes with n-oxides. Complexes with pyridine 1-oxide, 2,2′-bipyridine 1,1′-dioxide and 2,2′,2″-terpyridine 1,1′, 1″-trioxide. Inorg. Chim. Acta, 1982, 59, 133-140.
[35]
Collado, D.; Perez-Inestrosa, E.; Suau, R.; Desvergne, J.P.; Bouas-Laurent, H. Bis(isoquinoline N-oxide) pincers as a new type of metal cation dual channel fluorosensor. Org. Lett., 2002, 4(5), 855-858.
[36]
Dyker, G.; Holzer, B.; Henkel, G. A chiral bis-N-oxide isoelectronic with Jacobsen’s salen ligand. Tetrahedron Asymmetry, 1999, 10(17), 3297-3307.
[37]
Cerecetto, H.; Gerpe, A. ’ Gonzalez, M.; Aran, V.J.; de Ocariz, C.O. Pharmacological Properties of Indazole Derivatives: Recent Developments. Mini Rev. Med. Chem., 2005, 5(10), 869-878.
[38]
Mfuh, A.M.; Larionov, O.V. Heterocyclic N-Oxides – An emerging class of therapeutic agents. Curr. Med. Chem., 2015, 22(24), 2819-2857.
[39]
Dos Santos Fernandes, G.F.; Pavan, A.R.; Dos Santos, J.L. Heterocyclic N-oxides – A promising class of agents against tuberculosis, malaria and neglected tropical diseases. Curr. Pharm. Des., 2018, 24(12), 1325-1340.
[40]
Boyle, R.G.; Travers, S. N-oxide-containing pharmaceutical compounds. PCT patent, WO2008139152A1, November 20, 2008.
[41]
Mlostoń, G.; Romański, J.; Jasiński, M.; Heimgartner, H. Exploration of 4,5-dimethyl-1H-imidazole N-oxide derivatives in the synthesis of new achiral and chiral ionic liquids. Tetrahedron Asymmetry, 2009, 20(9), 1073-1080.
[42]
Pieczonka, A.M.; Mlostoń, G.; Heimgartner, H. Synthesis of bis-heterocyclic 1h‐imidazole 3‐oxides from 3‐oxido‐1h‐imidazole‐4‐carbohydrazides. Helv. Chim. Acta, 2012, 95(3), 404-414.
[43]
Mlostoń, G.; Mucha, P.; Heimgartner, H. Chiral Imidazoles and imidazole N-Oxides as ligands for stereoselective cyclopropanation reactions. Lett. Org. Chem., 2012, 9(2), 89-91.
[44]
Kwiatkowski, P.; Muchac, P.; Mlostoń, G.; Jurczak, J. Novel chiral C 2-Symmetric bisimidazole-n-oxides as promising organocatalysts for enantioselective allylation of aromatic aldehydes. Synlett, 2009, 11, 1757-1760.
[45]
Mloston, G.; Wroblewska, A.; Obijalska, E.; Heimgartner, H. Optically active imidazole N-oxides derived from L-prolinamine. Tetrahedron Asymmetry, 2013, 24(15-16), 958-965.
[46]
Mloston, G.; Urbaniak, K.; Wojciechowska, A.; Linden, A.; Heimgartner, H. Unexpected course of the reaction of 2-unsubstituted 1h-imidazole 3-oxides with ethyl acrylate. Helv. Chim. Acta, 2012, 95(4), 577-585.
[47]
Wroblewska, A.; Mloston, G.; Heimgartner, H. Synthesis of optically active polycyclic N-heterocycles derived from L-prolinamine. Tetrahedron Asymmetry, 2015, 26(8-9), 505-509.
[48]
Adiulin, E.I.; Kutasevich, A.V.; Mityanov, V.S.; Tkach, I.I.; Koldaeva, T.Y. Nucleophilic halogenation of imidazole N-oxides. Chem. Heterocycl. Compd., 2015, 51(5), 500-502.
[49]
Mloston, G.; Wroblewska, A.; Heimgartner, H. Synthesis of optically active trifluoromethyl-substituted 2,3-dihydroimidazo[2,1-b]oxazoles. J. Fluor. Chem., 2016, 189, 1-6.
[50]
Mityanov, V.S.; Kutasevich, A.V.; Krayushkin, M.M.; Lichitsky, B.V.; Dudinov, A.A.; Komogortsev, A.N.; Kuzmina, L.G. Condensation of imidazole N-oxide with Meldrum’s acid and aldehydes: a new method for C2-functionalization of 2-unsubstituted imidazole N-oxides. Tetrahedron Lett., 2016, 57(48), 5315-5316.
[51]
Hossain, M.; Pradhan, K.; Nanda, A.K. An expeditious synthetic protocol for chlorination of imidazole N-oxide: Synthesis of 2-chloroimidazoles. Tetrahedron Lett., 2017, 58(39), 3772-3776.
[52]
Ten, Y.A.; Salnikov, O.G.; Amitina, S.A.; Stass, D.V.; Rybalova, T.V.; Kazantsev, M.S. Bogomyakov, Artem S.; Mostovich, Evgeny A.; Mazhukin, Dmitrii G. The Suzuki-Miyaura reaction as a tool for modification of phenoxyl-nitroxyl radicals of the 4H-imidazole N-oxide series. RSC Advances, 2018, 8, 26099-26107.
[53]
Aguirre, G.; Boiani, M.; Cerecetto, H.; Gerpe, A.; Gonzalez, M.; Sainz, Y.F.; Denicola, A.; De Ocariz, C.O.; Nogal, J.J.; Montero, D. Novel antiprotozoal products: imidazole and benzimidazole N-oxide derivatives and related compounds. Arch. Pharm., 2004, 337(5), 259-270.
[54]
Nyerges, M.; Viranyi, A.; Zhang, W.; Groundwater, P.W.; Blasko, G.; Toke, L. Synthesis of indazole-N-oxides via the 1,7-electrocyclization of azomethine ylides. Tetrahedron, 2004, 60(44), 9937-9944.
[55]
Gerpe, A.; Piro, O.E.; Cerecetto, H.; Gonzalez, M. Structure of indazole N1-oxide derivatives studied by X-ray, theoretical methods, 1H, 13C, 15N NMR and EI/MS. J. Mol. Struct., 2007, 871(1-3), 98-107.
[56]
Gerpe, A.; Aguirre, G.; Boiani, L.; Cerecetto, H.; González, M.; Olea-Azar, C.; Rigol, C.; Maya, J.D.; Morello, A.; Piro, O.E.; Arán, V.J.; Azqueta, A.; de Ceráin, A.L.; Monge, A.; Rojas, M.A.; Yaluff, G. Indazole N-oxide derivatives as antiprotozoal agents: synthesis, biological evaluation and mechanism of action studies. Bioorg. Med. Chem., 2006, 14(10), 3467-3480.
[57]
Qu, S-J.; Liu, Q-W.; Tan, C-H.; Jiang, S-H.; Zhu, D-Y. New indole N-oxide alkaloids from Evodia fargesii. Planta Med., 2006, 72(3), 264-266.
[58]
Kaji, E.; Zen, S. Boron trifluoride-promoted transformation of 3,5-bis(methoxycarbonyl)-4-phenylisoxazoline N-oxide into 3H-indole N-oxide derivative. Heterocycles, 1979, 13(1), 187-190.
[59]
Canestrari, S.; Mar'in, A.; Sgarabotto, P.; Righi, L.; Greci, L. New insights on the reaction of trialkyl phosphites with 2-phenyl-3-phenylimino-3Hindole N-oxide: an indolic nitrone. Crystal structures of 1-diethylphosphoryl- 2-phenyl-3-phenylamino-1H-indole and 2-phenyl-4-phenylimino-4H-3,1- benzoxazine. J. Chem. Soc. Perkin 2,, 2000, 4, 833-838.
[60]
Greci, L.; Tommasi, G. Bruni, Paolo; Sgarabotto, P.; Righi, L. Diastereoselectivity in 1,3-dipolar cycloaddition reactions between indolic nitrones and electron-deficient alkenes. Eur. J. Org. Chem., 2001, 16, 3147-3153.
[61]
Lantsetti, N.A.; Ryabova, S.Y.; Alekseeva, L.M.; Shashkov, A.S.; Granik, V.G. Synthesis and properties of [1,4]diazepino[6,5-b]indoles. Russ. Chem. Bull., 2002, 51(3), 506-512.
[62]
Yamada, F.; Kawanishi, A.; Tomita, A.; Somei, M. The chemistry of indoles. 121. The first preparation of the unstable 1-hydroxy-2,3-dimethylindole, and structural determination of its air-oxidized product, 3-hydroxy-2,3-dimethyl-3H-indole N-oxide. ARKIVOC, 2003, (8), 102-111.
[63]
Roh, H.J.; Kim, G.; Cho, S.; Ryu, J.Y.; Lee, J.; Kim, J.N. Synthesis of isatin-conjugated 3H-indole-N-oxides and their serendipitous conversion to spiroindolenines. Tetrahedron Lett., 2018, 59(15), 1484-1488.
[64]
Pan, W.; Dong, D.; Sun, S.; Liu, Q. One-pot synthesis of substituted indole N-oxides: TiCl4-mediated Baylis-Hillman reaction of a-oxo cyclic ketene-S,S-acetal with ortho-nitrobenzaldehydes and subsequent intramolecular cyclization. Synlett, 2006, (7), 1090-1094.
[65]
Yang, Y.; Wang, X.; Li, Y.; Zhou, B.A. [4+1] Cyclative Capture Approach to 3H-Indole-N-oxides at Room Temperature by Rhodium(III)-Catalyzed C-H Activation. Angew. Chem. Int. Ed., 2015, 54(51), 15400-15404.
[66]
Hulme, C.; Mathew, R.; Moriarty, K.; Miller, B.; Ramanjulu, M.; Cox, P.; Souness, J.; Page, K.M.; Uhl, J.; Travis, J.; Labaudiniere, R.; Huang, F.; Djuric, S.W. Orally active indole N-oxide PDE4 inhibitors. Bioorg. Med. Chem. Lett., 1998, 8(21), 3053-3058.
[67]
Sugie, Y.; Hirai, H.; Inagaki, T.; Ishiguro, M.; Kim, Y.J.; Kojima, Y.; Sakakibara, T.; Sakemi, S.; Sugiura, A.; Suzuki, Y.; Brennan, L.; Duignan, J.; Huang, L.H.; Sutcliffe, J.; Kojima, N. A new antibiotic CJ-17665 from Aspergillus ochraceus. J. Antibiot. , 2001, 54(11), 911-916.
[68]
Igeta, H.; Tsuchiya, T.; Yamada, M.; Arai, H. Synthesis of pyridazine derivatives. IX. Photo-induced oxygenation of hydrocarbons by pyridazine N-oxide. Chem. Pharm. Bull., 1968, 16(4), 767-769.
[69]
Tsuchiya, T.; Arai, H.; Igeta, H. Photo-induced oxygenation by pyridazine N-oxide. II. Formation of epoxides from ethylenic compounds. Tetrahedron Lett., 1969, (32), 2747-2750.
[70]
Tang, Y.; He, C.; Imler, G.H.; Parrish, D.A.; Shreeve, J.M. Energetic 1,2,5-Oxadiazolo-Pyridazine and its N-Oxide. Chemistry Eur. J.,, 2017, 23(60), 15022-15025.
[71]
Altuntas, T.G.; Gorrod, J.W. The in vitro oxidation of isomeric aromatic diazines to mono-N-oxides. Pharm. Sci. Commun, 1994, 4(2), 117-124.
[72]
Igeta, H.; Tsuchiya, T.; Nakai, T. Reactions of pyridazine N-oxides with organometallic compounds. Tetrahedron Lett., 1969, (31), 2667-2670.
[73]
Kurita, J.; Kakusawa, N.; Yasuike, S.; Tsuchiya, T. Reaction of pyridazine N-oxides with pyridynes: formation of the first examples of pyrido-oxepins. Heterocycles, 1990, 31(11), 1937-1940.
[74]
Lian, Y.; Coffey, S.B.; Li, Q.; Londregan, A.T. Preparation of Heteroaryl Ethers from Azine N-Oxides and Alcohols. Org. Lett., 2016, 18(6), 1362-1365.
[75]
Roudesly, F.; Veiros, L.F.; Oble, J.; Poli, G. Pd-Catalyzed Direct C-H Alkenylation and Allylation of Azine N-Oxides. Org. Lett., 2018, 20(8), 2346-2350.
[76]
Leclerc, J-P.; Fagnou, K. Palladium-catalyzed cross-coupling reactions of diazine N-oxides with aryl chlorides, bromides, and iodides. Angew. Chem. Int. Ed., 2006, 45(46), 7781-7786.
[77]
Popp, C.J.; Garlough, G.D. Transition metal complexes of diazine N-oxides. J. Inorg. Nucl. Chem., 1981, 43(3), 501-507.
[78]
Kurita, J.; Kakusawa, N.; Yasuike, S.; Tsuchiya, T. Reaction of Pyridazine N-Oxides with Pyridynes: Formation of the First Examples of Pyrido-oxepins. Heterocycles, 1990, 31(11), 1937-1940.
[79]
Giorgio, B.; Cesare, C.; Gabriele, N.; Francesco, S. 17-(Pyridazine-N-oxide)- substituted steroidal compounds active on the cardiovascular system. European Patent EP0551953A2, January 16, 1992.
[80]
Ikekawa, N.; Honna, Y. Photochemical reactions of pyrazine N-oxides. Tetrahedron Lett., 1967, (13), 1197-1200.
[81]
Paudler, W.W.; Humphrey, S.A. Basicities and H-D exchange of pyrazine N-oxide. J. Org. Chem., 1970, 35(10), 3467-3470.
[82]
Uchimaree, F.; Okada, S.; Kosasayama, A.; Konno, T. Mass spectra of pyrazine N-oxide. Pyrazine derivatives. III. J. Heterocycl. Chem., 1971, 8(1), 99-104.
[83]
Okada, S.; Kosasayama, A.; Konno, T.; Uchimaru, F. Pyrazine derivatives. II. Synthesis, reactions, and spectra of pyrazine N-oxide derivatives. Chem. Pharm. Bull. , 1971, 19(7), 1344-1357.
[84]
Stanovnik, B.; Tišler, M.R.; Katritxky, A.; Denisko, O.V. The tautomerism of heterocycles. six-membered heterocycles: Part 1, annular tautomerism. Adv. Heterocycl. Chem., 2001, (81), 253-303.
[85]
Andersson, H.; Banchelin, T.S-L.; Das, S.; Gustafsson, M.; Olsson, R.; Almqvist, F. Complete regioselective addition of grignard reagents to pyrazine n-oxides, toward an efficient enantioselective synthesis of substituted piperazines. Org. Lett., 2010, 12(2), 284-286.
[86]
Aitken, R.A.; Fodi, B.; Palmer, M.H.; Slawin, A.M.Z.; Yang, J. Experimental and theoretical molecular and electronic structures of the N-oxides of pyridazine, pyrimidine and pyrazine. Tetrahedron, 2012, 68(29), 5845-5851.
[87]
Speca, A.N.; Karayannis, N.M.; Pytlewski, L.L.; Owens, C. Cobalt(II), nickel(II), and copper(II) nitrate complexes with pyrazine N-oxide. J. Inorg. Nucl. Chem., 1976, 38(1), 91-94.
[88]
Speca, A.N.; Karayannis, N.M.; Pytlewski, L.L. Transition metal perchlorate complexes with pyrazine N-oxide. J. Inorg. Nucl. Chem., 1973, 35(9), 3113-3128.
[89]
Vicentini, G.; Zinner, L.B. Pyrazine N-oxide adducts of some lanthanide perchlorates. Inorg. Nucl. Chem. Lett., 1974, 10(8), 629-635.
[90]
Alencar, F.L.; Matos, J.R.; Zinner, L.B. Pyrazine-N-oxide (pyzNO) complexes of lanthanide(III) trifluoroacetates (TFA). J. Alloys Compd., 1994, 207-208, 461-464.
[91]
Marinho, E.P.; Araujo Melo, D.M.; Zinner, L.B.; Vicentini, G.; Zukerman-Schpector, J.; Zinner, K. Hydrated neodymium(III) and europium(III) picrate complexes with pyrazine-N-oxide. J. Alloys Compd., 2000, 303-304, 116-1120.
[92]
Usui, I.; Lin, D.W.; Masuda, T.; Baran, P.S. Convergent synthesis and structural confirmation of phellodonin and sarcodonin ε. Org. Lett., 2013, 15(9), 2080-2083.
[93]
Tone, H.; Matoba, K.; Goto, F.; Torisawa, Y.; Nishi, T.; Minamikawa, J-I. Progress in the synthesis of opc-15161: easy access to dioxygenated pyrazine n-oxide structure. Org. Process Res. Dev., 2000, 4(5), 312-317.
[94]
Xia, Q.; Zhang, L.; Zhang, J.; Sheng, R.; Yang, B.; He, Q.; Hu, Y. Synthesis, hypoxia-selective cytotoxicity of new 3-amino-1,2,4-benzotriazine 1,4-dioxide derivatives. Eur. J. Med. Chem., 2011, 46(3), 919-926.
[95]
Chowdhury, G.; Sarkar, U.; Pullen, S.; Wilson, W.R.; Rajapakse, A.; Fuchs-Knotts, T.; Gates, K.S. DNA strand cleavage by the phenazine di-N-oxide natural product myxin under both aerobic and anaerobic conditions. Chem. Res. Toxicol., 2012, 25(1), 197-206.
[96]
Cugola, A.; Donati, D.; Guarneri, M.; Micheli, F.; Missio, A.; Pecunioso, A.; Reggiani, A.; Tarzia, G.; Zanirato, V. Synthesis and biological evaluation of pyrido[2,3-b]pyrazine and pyrido[2,3-b]pyrazine-N-oxide as selective glycine antagonists. Bioorg. Med. Chem. Lett., 1996, 6(22), 2749-2754.
[97]
Rusinov, V.L.; Kovalev, I.S.; Kozhevnikov, D.N.; Ustinova, M.M.; Chupakhin, O.N.; Pokrovskii, A.G.; Ilicheva, T.N.; Belanov, E.F.; Bormotov, N.I.; Serova, O.A.; Volkov, G.N. Synthesis and antiviral activity of 2-amino-3-ethoxycarbonylpyrazine derivatives. Pharm. Chem. J., 2005, 39(12), 630-635.
[98]
Cresswell, R.M.; Maurer, H.K.; Strauss, T.; Brown, G.B. Purine N-Oxides. XIV. A Total synthesis of a Pyrimidine N-Oxide, a Pteridine 1-N-Oxide, and Xanthine 3-N-Oxide. J. Org. Chem., 1965, 30(2), 408-410.
[99]
Delia, T.J.; Venton, D.L. Pyrimidine N-oxide. Preparation of 6-chloro-2,4-diaminopyrimidine 3-N-oxide and its reactions. J. Heterocycl. Chem., 1972, 9(1), 73-75.
[100]
Muller, J.C.; Ramuz, H.; Wagner, H.P. A new route to the synthesis of 2-amino-6-(methoxycarbonyl)amino-4-(tetrahydropyridyl)pyrimidine 1-oxide. Helv. Chim. Acta, 1983, 66(3), 809-813.
[101]
Yamanaka, H.; Sakamoto, T.; Niitsuma, S. Pyrimidine N-oxides: syntheses, structures, and chemical properties. Heterocycles, 1990, 31(5), 923-967.
[102]
Ranjbar, M.; Celik, O.; Mahmoudi, N.; Heydar, S.; Sheshmani, S.; Mobarakeh, N.A. Synthesis of lead(ii) minoxidil coordination polymer: A new precursor for lead(ii) oxide and lead(ii) hydroxyl bromide. J. Inorg. Organomet. Polym., 2012, 22(4), 837-844.
[103]
Hirshey, S.J.; Falany, C.N. Purification and characterization of rat liver minoxidil sulphotransferase. Biochem. J., 1990, 270(3), 721-728.
[104]
Youssif, S. Recent trends in the chemistry of pyridine N-oxides. ARKIVOC, 2001, (1), 242-268.
[105]
Zhang, L.; Cole, J.M. Anchoring groups for dye-sensitized solar cells. ACS Appl. Mater. Interfaces, 2015, 7(6), 3427-3455.
[106]
Liu, Y.; Liu, D.; Wang, C. Bivalent metal-based MIL-53 analogues: Synthesis, properties and application. J. Solid State Chem., 2015, 223, 84-94.
[107]
Shiina, I. An adventurous synthetic journey with MNBA from its reaction chemistry to the total synthesis of natural products. Bull. Chem. Soc. Jpn., 2014, 87(2), 196-233.
[108]
Odani, R.; Hirano, K.; Satoh, T.; Miura, M. Copper-mediated formally dehydrative biaryl coupling of azine N-Oxides and oxazoles. J. Org. Chem., 2015, 80(4), 2384-2391.
[109]
Chen, Y. g; Huang, J.; Hwang, T.-L.; Chen, M.J.; Tedrow, J.S.; Farrell, R.P.; Bio, M.M.; Cui, S. Highly regioselective halogenation of pyridine N-oxide: Practical access to 2-halo-substituted pyridines. Org. Lett., 2015, 17(12), 2948-2951.
[110]
Cenacchi, V.; Battaglia, R.; Cinato, F.; Riccardi, B.; Spinabelli, D.; Brogin, G.; Puccini, P.; Pezzetta, D. In vitro and in vivo metabolism of CHF 6001, a selective phosphodiesterase (PDE4) inhibitor. Xenobiotica, 2015, 45(8), 693-710.
[111]
Ishihara, K.; Lu, Y. Boronic acid-DMAPO cooperative catalysis for dehydrative condensation between carboxylic acids and. Chem. Sci., 2016, 7(2), 1276-1280.
[112]
Brugarolas, P.; Freifelder, R.; Cheng, S-H.; DeJesus, O. Synthesis of meta-substituted [18F]3-fluoro-4-aminopyridine via direct radiofluorination of pyridine N-oxides. Chem. Commun. , 2016, 52(44), 7150-7152.
[113]
Saikia, B.; Khatioda, R.; Bora, P.; Sarma, B. Pyridine N-oxides as coformers in the development of drug cocrystals. CrystEngComm, 2016, 18(43), 8454-8464.
[114]
Kaieda, A.; Takahashi, M.; Takai, T.; Goto, M.; Miyazaki, T.; Hori, Y.; Unno, S.; Kawamoto, T.; Tanaka, T.; Itono, S.; Takagi, T.; Hamada, T.; Shirasaki, M.; Okada, K.; Snell, G.; Bragstad, K.; Sang, B.C.; Uchikawa, O.; Miwatashi, S. Structure-based design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine-based p38 MAP kinase inhibitors. Bioorg. Med. Chem., 2018, 26(3), 647-660.
[115]
Balzarini, J.; Stevens, M.; De Clercq, E.; Schols, D.; Pannecouque, C. Pyridine N-oxide derivatives: unusual anti-HIV compounds with multiple mechanisms of antiviral action. J. Antimicrob. Chemother., 2005, 55, 135-138.
[116]
Fallahpour, R-A.; Neuburger, M. An efficient, easy route for the synthesis of 2,2′:6′,2”-terpyridine 1′-oxides. Eur. J. Org. Chem., 2001, 10, 1853-1856.
[117]
Amoroso, A.J.; Burrows, M.W.; Haigh, R.; Hatcher, M.; Jones, M.; Kynast, U.; Malik, K.M.; Sendor, D. The synthesis and characterisation of europium terpyridine-N-oxide complexes. Dalton Trans., 2007, 16, 1630-1638.
[118]
Amoroso, A.J.; Burrows, M.W.; Coles, S.J.; Haigh, R.; Farley, R.D.; Hursthouse, M.B.; Jones, M.; Malik, K.M.; Murphy, D.M. The synthesis and structure of terpyridine-N-oxide complexes of copper(II) perchlorate. Dalton Trans., 2008, 0, 506-513.
[119]
Amoroso, A.J.; Burrows, M.W.; Dickinson, A.A.; Jones, C.; Willock, D.J.; Wong, W-T. Geometrical preferences of complexes of terpyridine N-oxide ligands: synthesis and crystal structures of nickel(II) with terpyridine 1,1′,1”-trioxide, terpyridine 1,1”-dioxide and terpyridine 1-oxide. Dalton Trans., 2001, 0, 225-227.
[120]
Lopez, J.P.; Kraus, W.; Reck, G.; Thuenemann, A.; Kurth, D.G. Synthesis, structure and reactivity of the homoleptic iron(II) complex of the novel 4′-(4”'-pyridyl-N-oxide)-2,2′:6′,2”-terpyridine ligand. Inorg. Chim. Acta, 2005, 358(12), 3384-3390.
[121]
Hamaguchi, T.; Inoue, Y.; Ujimoto, K.; Ando, I. Synthesis, crystal structure and electrochemistry of a ruthenium complex coordinated with an ambidentate 2-mercaptopyridinato N-oxide ligand. Polyhedron, 2008, 27(9-10), 2031-2034.
[122]
Wong, W-L.; Lee, W-S.; Kwong, H-L. Synthesis of new chiral terpyridine mono-N-oxide and di-N-oxide ligands and their applications in coppercatalyzed asymmetric cyclopropanation. Tetrahedron Asymmetry, 2002, 13(14), 1485-1492.
[123]
Wong, W-L.; Lee, C-S.; Leung, H-K.; Kwong, H-L. The first series of chiral 2,2′:6′,2”-terpyridine tri-N-oxide ligands for Lewis base-catalyzed asymmetric allylation of aldehydes. Org. Biomol. Chem., 2004, 2, 1967-1969.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 23
ISSUE: 5
Year: 2019
Page: [616 - 627]
Pages: 12
DOI: 10.2174/1385272823666190408095257
Price: $58

Article Metrics

PDF: 26
HTML: 4
PRC: 1

Special-new-year-discount