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Molecular Diversity

, Volume 22, Issue 4, pp 919–927 | Cite as

4-Amino-2,3-dihydro-1λ6-isothiazole-1,1-dioxides and their chemical properties evaluation

  • Maksim S. Dyachenko
  • Alexey V. DobrydnevEmail author
  • Yulian M. Volovenko
Original Article
  • 46 Downloads

Abstract

The reactivity of the 4-amino-2,3-dihydro-1H-1λ6-isothiazole-1,1-dioxide (β-amino-γ-sultam) framework has not been studied sufficiently. Here we describe the chemical properties of this heterocyclic system toward electrophiles on spiranic and non-spiranic substrates. A variety of C-electrophiles (acetic anhydride, benzoyl chloride, DMFDMA, 4,4-dimethoxybutan-2-one) and heteroatom electrophiles (bromine, nitrosyl acetate) have been explored. Both the C-5 and 4-amino positions of the β-amino-γ-sultam system are able to undergo electrophilic reactions. Heteroatom electrophiles attack the C-5 position, whereas carbo-electrophiles affect the amino group. β-Amino-γ-sultams also were used as starting compounds for the synthesis of 6- or 7-substituted 1λ6-isothiazolo[4,5-b]pyridine-1,1-dioxides through condensation reaction and palladium-catalyzed oxidative coupling.

Graphical abstract

Keywords

Sulfonamides Spiro compounds Enamines Electrophiles Cyclization Coupling 

Notes

Acknowledgements

Alexey Dobrydnev acknowledges Dr. Demid. S. Milokhov for a fellowship and technical support. We would also like to show our gratitude to Mr. Mit Dobrydnev for sharing his pearls of wisdom with us during the course of this research.

Supplementary material

11030_2018_9848_MOESM1_ESM.pdf (7.4 mb)
Supplementary material 1 (PDF 7609 kb)

References

  1. 1.
    Huang C-Y, Doyle AG (2015) Electron-deficient olefin ligands enable generation of quaternary carbons by Ni-catalyzed cross-coupling. J Am Chem Soc 137:5638–5641.  https://doi.org/10.1021/jacs.5b02503 CrossRefPubMedGoogle Scholar
  2. 2.
    Spaltenstein A, Almond MR, Bock WJ, Cleary DG, Furfine ES, Hazen RJ, Kazmierski WM, Salituro FG, Tung RD, Wright LR (2000) Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds. Bioorg Med Chem Lett 11:1159–1162.  https://doi.org/10.1016/S0960-894X(00)00163-3 CrossRefGoogle Scholar
  3. 3.
    Cherney RJ, Mo R, Meyer DT, Hardman KD, Liu RQ, Covington MB, Qian M, Asserman ZR, Christ DD, Trzaskos JM, Newton RC, Decicco CP (2004) Sultam hydroxamates as novel matrix metalloproteinase inhibitors. J Med Chem 47:2981–2983.  https://doi.org/10.1021/jm049833g CrossRefPubMedGoogle Scholar
  4. 4.
    Binder D (1987) Thieno-1,2-thiazole derivatives, process for their preparation, and pharmaceutical compositions containing them. Chem Abstr 107:96709. EP Patent 0,213,295Google Scholar
  5. 5.
    Abou-Gharbia MA, Schiehser GA, Childress SJ (1988) Piperazinoisothiazolones with psychotropic activity. Chem Abstr 108:112497. US Patent 4,732,984Google Scholar
  6. 6.
    Gymer GE, Narayanaswami S, Richardson K (1990) Triazole antifungal agents. Chem Abstr 113:40728. EP Patent 0,352,946Google Scholar
  7. 7.
    Anderson DJ, Hester JB Jr (2001) Antibiotic sultam and sultone derived oxazolidinones. Chem Abstr 134:340497. WO Patent 2,001,032,657Google Scholar
  8. 8.
    Carty TJ, Marfat A, Moore PF, Falkner FC, Twomey TM, Weissman A (1993) Ampiroxicam, an anti-inflammatory agent which is a prodrug of piroxicam. Agents Actions 39:157–165.  https://doi.org/10.1007/BF01998969 CrossRefPubMedGoogle Scholar
  9. 9.
    Hansen JM, Kristensen M, Skovsted L (1968) Sulthiame (Ospolot®) as inhibitor of diphenylhydantoin metabolism. Epilepsia 9:17–22.  https://doi.org/10.1111/j.1528-1157.1968.tb04954.x CrossRefPubMedGoogle Scholar
  10. 10.
    Brozozowski F, Saczewski F, Neamati N (2006) Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine-dioxides. Bioorg Med Chem Lett 16:5298–5302.  https://doi.org/10.1016/j.bmcl.2006.07.089 CrossRefGoogle Scholar
  11. 11.
    Ingate ST, Marco JL, Witvrouw M, Pannecouque C, De Clercq E (1997) Studies into the synthesis of derivatives of 4-amino-2,3-dihydroisothiazole 1,1-dioxides and 4-amino-1,2-oxathiole 2,2-dioxides: the search for linked π-system containing analogues as potential inhibitors of HIV-1 reverse transcriptase. Tetrahedron 53:17795–17814.  https://doi.org/10.1016/S0040-4020(97)10244-7 CrossRefGoogle Scholar
  12. 12.
    Van Nhien AN, Tomassi C, Len C, Marco-Contelles JL, Balzarini J, Pannecouque C, De Clercq E, Postel D (2005) First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO on HIV-1 replication. J Med Chem 48:4276–4284.  https://doi.org/10.1021/jm050091g CrossRefGoogle Scholar
  13. 13.
    de Castro S, Peromingo MT, Lozano AE, Camarasa M-J, Velázquez S (2008) Reactivity of the 4-amino-5H-1,2-oxathiole-2,2-dioxide heterocyclic system: a combined experimental and theoretical study. Chem Eur J 14:9620–9632.  https://doi.org/10.1002/chem.200800433 CrossRefPubMedGoogle Scholar
  14. 14.
    de Castro S, Familiar O, Andrei G, Snoeck R, Balzarini J, Camarasa M-J, Velázquez S (2011) From β-amino-γ-sultone to unusual bicyclic pyridine and pyrazine heterocyclic systems: synthesis and cytostatic and antiviral activities. Chem Med Chem 6:686–697.  https://doi.org/10.1002/cmdc.201000546 CrossRefPubMedGoogle Scholar
  15. 15.
    Dobrydnev AV, Popova MV, Saffon-Merceron N, Listunov D, Volovenko YM (2015) Synthesis of the first representatives of spiro-1λ6-isothiazolidine-1,1,4-triones. Synthesis 47:2523–2528.  https://doi.org/10.1055/s-0034-1380434 CrossRefGoogle Scholar
  16. 16.
    Popova MV, Dobrydnev AV, Dyachenko MS, Duhayon C, Listunov D, Volovenko YuM (2017) Synthesis of a series of tetraminic acid sulfone analogs. Monats Chem 148:939–946.  https://doi.org/10.1007/s00706-016-1884-6 CrossRefGoogle Scholar
  17. 17.
    Hirota K, Kuki H, Maki Y (1994) Novel synthesis of pyrido[3,4-d]pyrimidines, pyrido[2,3-d]pyrimidines, and quinazolines via palladium-catalyzed oxidative coupling. Heterocycles 37:563–570.  https://doi.org/10.3987/COM-93-S99 CrossRefGoogle Scholar
  18. 18.
    Perrin DD, Armarego IF, Perrin DR (1980) Purification of laboratory chemicals, 2nd edn. Pergamon Press, New YorkGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Maksim S. Dyachenko
    • 1
    • 2
  • Alexey V. Dobrydnev
    • 1
    • 3
    Email author
  • Yulian M. Volovenko
    • 1
  1. 1.Chemistry DepartmentTaras Shevchenko National University of KyivKievUkraine
  2. 2.Enamine Ltd.KievUkraine
  3. 3.SMC Ecopharm Ltd.KievUkraine

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