1,2-Benzoxathiin-4(3H)-one 2,2-dioxide – an underinvestigated building block with a high synthetic and pharmacological potential: synthesis, chemical properties, biological activity

Authors

DOI:

https://doi.org/10.24959/ophcj.21.234271

Keywords:

sultone; oxathiine; heterocyclization; active methylene ketones; biological activity

Abstract

Aim. To analyze the available literature data on the methods of synthesis, chemical transformations and the biological activity of derivatives containing a sultone core – 1,2-benzoxathiin-4(3H)-one 2,2-dioxide – and to show the possibilities of their further use in the construction of new molecular systems with attractive pharmacological properties.

Results and discussion. The most widespread method for the synthesis of 1,2-benzoxathiin-4(3H)-one 2,2-dioxides is the cyclization of salicylic acid derivatives. The known chemical transformations of 1,2-benzoxathiin-4(3H)-one 2,2-dioxides deal with all reaction centers of the heterocyclic fragment of the condensed system – C=O and CH2 groups, SO2–O bond, CH2CO fragment as a whole. It should be noted that the oxathiine nucleus is prone to undergo recyclizations. The use of 1,2-benzoxathiin-4(3H)-one 2,2-dioxides in multicomponent transformations still remains hardly explored. The “abnormal” course of some classical transformations involving 1,2-benzoxathiine 2,2-dioxides is also noteworthy. The study of the pharmacological properties of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide derivatives is scarce and mainly based on their structural similarity to the coumarin core, which led to the study of anticoagulant, antimicrobial and antitumor properties for the sultone derivatives.

Conclusions. The analysis has shown a limited number of studies in each aspect – approaches to the synthesis of 1,2-benzoxathiin-4(3H)-one 2,2-dioxides, their chemical transformations and the study of their pharmacological activity. In addition to a small number of publications on this heterocyclic system, there have been almost no sultone studies in the last 20 years. Taking this into account 1,2-benzoxathiin-4(3H)-one 2,2-dioxide and its derivatives deserve close attention as objects of research for experimental chemistry and pharmacology.

References

Markitanov, Y. M.; Timoshenko, V. M.; Shermolovich, Y. G. β-Keto sulfones: preparation and application in organic synthesis. Journal of Sulfur Chemistry 2014, 35 (2), 188 – 236. https://doi.org/10.1080/17415993.2013.815749.

Roberts, D. W. Sulfonation Technology for Anionic Surfactant Manufacture. Org. Process Res. Dev. 1998, 2 (3), 194 – 202. https://doi.org/10.1021/op9700439.

De Castro, S.; García-Aparicio, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Camarasa, M.-J.; Velázquez, S. 4-Benzyloxy-γ-Sultone Derivatives: Discovery of a Novel Family of Non-Nucleoside Inhibitors of Human Cytomegalovirus and Varicella Zoster Virus. J. Med. Chem. 2009, 52 (6), 1582 – 1591. https://doi.org/10.1021/jm8014662.

de Castro, S.; Lobatón, E.; Pérez-Pérez, M.-J.; San-Félix, A.; Cordeiro, A.; Andrei, G.; Snoeck, R.; De Clercq, E.; Balzarini, J.; Camarasa, M.-J.; Velázquez, S. Novel [2‘,5‘-Bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]-3’-spiro-5’’-(4’’-amino-1’’,2’’-oxathiole-2’’,2’’-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity. J. Med. Chem. 2005, 48 (4), 1158 – 1168. https://doi.org/10.1021/jm040868q.

Xu, Y.; Zhang, Z.; Shi, J.; Liu, X.; Tang, W. Recent developments of synthesis and biological activity of sultone scaffolds in medicinal chemistry. Arabian Journal of Chemistry 2021, 14 (4), 103037. https://doi.org/10.1016/j.arabjc.2021.103037.

Mondal, S. Recent Developments in the Synthesis and Application of Sultones. Chem. Rev. 2012, 112 (10), 5339 – 5355. https://doi.org/10.1021/cr2003294.

Ali, G.; Subhan, F.; Khan, I.; Islam, N. U. Input of Isosteric and Bioisosteric Approach in Drug Design. J. Chem. Soc. Pak. 2014, 36 (1), 150 – 169.

Thornber, C. W. Isosterism and molecular modification in drug design. Chem. Soc. Rev. 1979, 8 (4), 563 – 580. https://doi.org/10.1039/CS9790800563.

Au, N.; Rettie, A. E. Pharmacogenomics of 4-Hydroxycoumarin Anticoagulants. Drug Metabolism Reviews 2008, 40 (2), 355 – 375. https://doi.org/10.1080/03602530801952187.

Ukrainets, I. V.; Petrushova, L. A.; Dzyubenko, S. P.; Sim, G. 2,1-Benzothiazine 2,2-Dioxides. 3*. 4-Hydroxy-1-Methyl-2,2-Dioxo-N-(1,3-Thiazol-2-yl)-1Н-2λ6,1-Benzothiazine-3-Carboxamides – a New Group of Potential Analgetics. Chem. Heterocycl. Comp. 2014, 50 (1), 103 – 110. https://doi.org/10.1007/s10593-014-1452-0.

Lega, D. A.; Filimonova, N. I.; Zupanets, I. A.; Shebeko, S. K.; Chernykh, V. P.; Shemchuk, L. A. Synthesis, anti-inflammatory, analgesic and antimicrobial activities of ethyl 2-amino-4-alkyl-4,6-dihydropyrano[3,2-c][2,1]benzothiazin-3-carboxylate 5,5-dioxides and triethylammoniun 3-[(4-hydroxy-1-ethyl-2,2-dioxido-1H-2,1-benzothiazin-3-yl)alkyl]-1-ethyl-1H-2,1-benzothiazin-5-olat 2,2-dioxides. Journal of Organic and Pharmaceutical Chemistry 2016, 14 (4), 3 – 11. https://doi.org/10.24959/ophcj.16.900.

Majumdar, K. C.; Mondal, S.; Ghosh, D. Synthesis of tricyclic and tetracyclic sultones by Pd-catalyzed intramolecular cyclization. Tetrahedron Lett. 2009, 50 (33), 4781 – 4784. https://doi.org/10.1016/j.tetlet.2009.06.028.

Metz, P.; Fleischer, M. Intramolecular Diels-Alder Reaction of Vinylsulfonates Possessing an Acyclic Diene Moiety. Synlett 1993, 1993 (06), 399 – 400. https://doi.org/10.1055/s-1993-22469.

Karsch, S.; Freitag, D.; Schwab, P.; Metz, P. Ring Closing Metathesis in the Synthesis of Sultones and Sultams. Synthesis 2004, 2004 (10), 1696 – 1712. https://doi.org/10.1055/s-2004-822408.

Karsch, S.; Schwab, P.; Metz, P. Synthesis of Sultones by Ring Closing Metathesis. Synlett 2002, 2002 (12), 2019 – 2022. https://doi.org/10.1055/s-2002-35560.

John, J. P.; Novikov, A. V. Selective Formation of Six-Membered Cyclic Sulfones and Sulfonates by C−H Insertion. Org. Lett. 2007, 9 (1), 61 – 63. https://doi.org/10.1021/ol062592h.

Wolckenhauer, S. A.; Devlin, A. S.; Du Bois, J. δ-Sultone Formation Through Rh-Catalyzed C−H Insertion. Org. Lett. 2007, 9 (21), 4363 – 4366. https://doi.org/10.1021/ol701950d.

Uno, H.; Kurokawa, M. Studies on 3-Substituted 1, 2-Benzisoxazole Derivatives. VII. Catalytic Reduction of 3-Sulfamoylmethyl-1, 2-benzisoxazole and Reactions of the Resulting Products. Chem. Pharm. Bull. 1982, 30 (1), 333 – 335. https://doi.org/10.1248/cpb.30.333.

King, L. C.; Ostrum, G. K. Selective Bromination with Copper(II) Bromide. J. Org. Chem. 1964, 29 (12), 3459 – 3461. https://doi.org/10.1021/jo01035a003.

Barbieri, W.; Bernardi, L.; Coda, S.; Vigevani, A. Synthesis and reactions of 1,2-benzoxathian-4-one 2-oxides. Tetrahedron Lett. 1971, 12 (52), 4913 – 4914. https://doi.org/10.1016/S0040-4039(01)97587-2.

Meyer, R. F. Some novel cyclizations of propiophenones with chlorosulfonic acid. J. Heterocycl. Chem. 1966, 3 (2), 174 – 177. https://doi.org/10.1002/jhet.5570030213.

Claney, J.; Alice, G.; Timoney, R. Int. J. Sulfur Chem., Part A. 1972, 2, 249 – 255.

Rehse, K.; Tenczer, J. Gerinnungsphysiologische Aktivität von 1,2-Benzoxathiinen. Arch. Pharm. 1980, 313 (3), 249 – 254. https://doi.org/10.1002/ardp.19803130310.

Grandane, A.; Belyakov, S.; Trapencieris, P.; Zalubovskis, R. Facile synthesis of coumarin bioisosteres—1,2-benzoxathiine 2,2-dioxides. Tetrahedron 2012, 68 (27), 5541 – 5546. https://doi.org/10.1016/j.tet.2012.04.080.

Grandane, A.; Tanc, M.; Zalubovskis, R.; Supuran, C. T. 6-Triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrases IX and XII. Bioorg. Med. Chem. Lett. 2014, 24 (5), 1256 – 1260. https://doi.org/10.1016/j.bmcl.2014.01.076.

Grandane, A.; Tanc, M.; Di Cesare Mannelli, L.; Carta, F.; Ghelardini, C.; Žalubovskis, R.; Supuran, C. T. 6-Substituted Sulfocoumarins Are Selective Carbonic Anhdydrase IX and XII Inhibitors with Significant Cytotoxicity against Colorectal Cancer Cells. J. Med. Chem. 2015, 58 (9), 3975 – 3983. http://doi.org/10.1021/acs.jmedchem.5b00523.

Grandane, A.; Tanc, M.; Žalubovskis, R.; Supuran, C. T. Synthesis of 6-aryl-substituted sulfocoumarins and investigation of their carbonic anhydrase inhibitory action. Bioorg. Med. Chem. 2015, 23 (7), 1430 – 1436. https://doi.org/10.1016/j.bmc.2015.02.023.

Schwender, Ch. F.; Sunday, B. R. 1,2-Benzoxathiin-2,2-dioxides. US4116961A, Sep 26, 1978.

Cecchetti, V.; Fravolini, A.; Fringuelli, R.; Schiaffella, F. New Heterocyclic Ring System. XIV. 7,11-Dithiaoxasteroids Analogues. Heterocycles 1984, 22 (10), 2293 – 2300. https://doi.org/10.3987/R-1984-10-2293.

Arava, V. R.; Siripalli, U. B. R.; Nadkarni, V.; Chinnapillai, R. Beilstein J. Org. Chem. 2007, 3 (20). https://doi.org/10.1186/1860-5397-3-20.

Allegrini, P.; Bologna, A.; Castaldi, G.; Lucchini, V.; Mantegazza, S.; Razzetti, G. Process for the preparation of benzo[d]isoxazol-3-yl-methanesulfonic acid and the intermediates thereof. US20080081914A1, Apr 03, 2008.

Peixoto, C.; Laurin, P.; Klich, M.; Dupuis-Hamelin, C.; Mauvais, P.; Lassaigne, P.; Bonnefoy, A.; Musicki, B. Synthesis of isothiochroman 2,2-dioxide and 1,2-benzooxathiin 2,2-dioxide gyrase B inhibitors. Tetrahedron Lett. 2000, 41 (11), 1741 – 1745. https://doi.org/10.1016/S0040-4039(00)00044-7.

Löwe, W.; Müller-Menke, C. Notiz zur Synthese von 1,2-Benzoxathiin-2,2-dioxid-Derivaten aus 3-Chromonsulfonsäure. Liebigs Ann. Chem. 1984, 1984 (7), 1395 – 1397. https://doi.org/10.1002/jlac.198419840716.

Löwe, W.; Matzanke, N.; Rütjes, T. Synthesen von Chromon-3-sulfonylharnstoffen. Arch. Pharm. 1994, 327 (12), 819 – 823. https://doi.org/10.1002/ardp.19943271213.

Löwe, W.; Jeske, P. 3,4-Dihydro-6-methyl-1,2-benzoxathiin-2,2-dioxid-Derivate mit Enaminketon-Strukturen aus 6-Methyl-4-chromon-3-sulfonsäure-phenylester. Liebigs Ann. Chem. 1985, 1985 (10), 2012 – 2016. https://doi.org/10.1002/jlac.198519851009.

Löwe, W.; Jeske, P. Umsetzungen von 4-Chromon-3-sulfonsäure-phenylester mit Amidinen. Liebigs Ann. Chem. 1986, 1986 (6), 1124 – 1126. https://doi.org/10.1002/jlac.198619860617.

Löwe, W.; Braden, T. Umsetzung von aromatischen Enaminonen mit Chlorsulfonsäure. Arch. Pharm. 1991, 324 (6), 385 – 387. https://doi.org/10.1002/ardp.19913240614.

Ghandi, M.; Bozcheloei, A. H.; Nazari, S. H.; Sadeghzadeh, M. Solvent-Dependent Reactions for the Synthesis of β-Keto-Benzo-δ-Sultone Scaffolds via DBU-Catalyzed O-Sulfonylation/Intramolecular Baylis–Hillman/1,3-H Shift or Dehydration Tandem Sequences. J. Org. Chem. 2011, 76 (24), 9975 – 9982. http://doi.org/10.1021/jo201506d.

Ghandi, M.; Taghi Nazeri, M.; Kubicki, M. An efficient one-pot, regio- and stereoselective synthesis of novel pentacyclic-fused pyrano[3,2-c]chromenone or quinolinone benzosultone derivatives in water. Tetrahedron 2013, 69 (24), 4979 – 4989. https://doi.org/10.1016/j.tet.2013.04.018.

Li, B.; Yan, W.; Zhang, C.; Zhang, Y.; Liang, M.; Chu, F.; Gong, Y.; Xu, B.; Wang, P.; Lei, H. New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA. Molecules 2015, 20 (3), 4307 – 4318. https://doi.org/10.3390/molecules20034307.

Löwe, W.; Müller-Menke, C. Reaktionen des 4-Hydroxy-1,2-benzoxathiin-3-carbaldehyd-2,2-dioxids mit Aminen und Hydrazinen. Arch. Pharm. 1988, 321 (10), 755 – 756. https://doi.org/10.1002/ardp.19883211013.

Löwe, W.; Müller-Menke, C. 1,2-Benzoxathiino[4,3-d]pyrimidin-5,5-dioxide. Arch. Pharm. 1985, 318 (10), 954 – 956. https://doi.org/10.1002/ardp.19853181019.

Löwe, W.; Jeske, P.; Kradepohl, A. An unusual ring transformation: Reaction of phenyl 4-chromone-3-sulfonate with methyl 3-aminocrotonate. J. Heterocycl. Chem. 1988, 25 (2), 699 – 701. https://doi.org/10.1002/jhet.5570250263.

Löwe, W.; Kradepohl, A. Michael additions with an enaminoester: Reaction of phenyl 4-chromone-3-sulfonate with methyl 3-amino-2-pentenoate. J. Heterocycl. Chem. 1989, 26 (3), 753 – 756. https://doi.org/10.1002/jhet.5570260345.

Löwe, W.; Kradepohl, A. 1,2- und 1,4-Additionen methylen-aktiver Verbindungen an ein heterocyclisches Enaminon. Arch. Pharm. 1990, 323 (12), 987 – 989. https://doi.org/10.1002/ardp.19903231209.

Löwe, W.; Göbel, S.; Müller-Menke, C. Über eine Benzoxathiin-Chromon-Ringtransformation. Arch. Pharm. 1988, 321 (10), 729 – 730. https://doi.org/10.1002/ardp.19883211006.

Grygoriv, G. V.; Lega, D. A.; Chernykh, V. P.; Zaprutko, L.; Gzella, A. K.; Pawełczyk, A.; Shemchuk, L. A. 1,2-Benzoxathiin-4(3H)-one 2,2-dioxide – new enol nucleophile in three-component interaction with benzaldehydes and active methylene nitriles. RSC Adv. 2018, 8, 37295 – 37302. https://doi.org/10.1039/c8ra06801a.

Grygoriv, G. V.; Lega, D. A.; Zaprutko, L.; Gzella, A. K.; Wieczorek-Dziurla, E.; Chernykh, V. P.; Shemchuk, L. A. Synthesis of novel spiro-condensed 2-amino-4H-pyrans based on 1,2-benzoxathiin-4(3H)-one 2,2-dioxide. Chem. Heterocycl. Comp. 2019, 55 (3), 254 – 260. https://doi.org/10.1007/s10593-019-02450-4.

Grygoriv, G. V.; Lega, D. A.; Zupanets, I. A.; Shebeko, S. K.; Zimin, S. M.; Starchikova, I. L.; Shemchuk, L. A. Spiro[benzo[е]pyrano[3,2-c][1,2]oxathiin-4,3’-indolil]-3-carbonitrile 5,5-dioxides: synthesis and the biological activity study. Journal of Organic and Pharmaceutical Chemistry 2019, 17 (4), 53 – 61. https://doi.org/10.24959/ophcj.19.182954.

Grygoriv, G. V.; Lega, D. O.; Chernykh, V. P.; Osolodchenko, T. P.; Shemchuk, L. A. Synthesis of 1,2-benzoxathiine 2,2-dioxide derivatives using aliphatic aldehydes and assessment of their antimicrobial activity. Journal of Organic and Pharmaceutical Chemistry 2017, 15 (4), 33 – 10. https://doi.org/10.24959/ophcj.17.927.

Grygoriv, G.; Lega, D.; Chernykh, V.; Osolodchenko, T.; Shemchuk L. Cycloalkanecarbaldehydes in synthesis of novel 1,2-benzoxathiin4(3H)-one 2,2-dioxide derivatives and study of the antimicrobial activity of synthesized compounds. ScienceRise: Pharmaceutical Science 2017, 6, 4 – 10. https://doi.org/10.15587/2519-4852.2017.119279.

Grygoriv, G. V.; Lega, D. A.; Chernykh, V. P.; Osolodchenko, T. P.; Shemchuk L. A. Domino-reactions of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide, hetarenecarbaldehydes and active methylene nitriles in the construction of new 2-amino-4H-pyrans and investigation of their antimicrobial properties. Journal of Organic and Pharmaceutical Chemistry 2018, 16 (1), 3 – 10. https://doi.org/10.24959/ophcj.18.931.

Grygoriv, G. V.; Lega, D. A.; Shemchuk, L. M.; Maloshtan, L. M.; Kalenichenko, G. S.; Chernykh, V. P.; Shemchuk, L. A. The synthesis of 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides and the study of their effect on the blood coagulation process. News of Pharmacy 2018, 4, 3 – 8. https://doi.org/10.24959/nphj.18.2224.

Lega, D. A.; Gorobets, N. Y.; Chernykh, V. P.; Shishkina, S. V.; Shemchuk, L. A. Peculiarities of 2-amino-3-R-4-aryl-4H-pyranes multicomponent synthesis derived from 1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide. RSC Adv. 2016, 6 (19), 16087 – 16099. https://doi.org/10.1039/c5ra24566d.

Lega, D. A.; Chernykh, V. P.; Shemchuk, L. A. The study of three-component interaction between 1-ethyl-1H-2,1-benzothiazin-4(3H)-one 2,2-dioxide, heterylcarbaldehydes and active methylene nitriles. Journal of Organic and Pharmaceutical Chemistry 2016, 14 (1), 6 – 16. https://doi.org/10.24959/ophcj.16.876.

Downloads

Published

2021-06-23

Issue

Section

Articles