Advertisement

Monatshefte für Chemie - Chemical Monthly

, Volume 148, Issue 12, pp 2173–2182 | Cite as

Synthesis, characterization, crystal structure, and antituberculosis activity of some novel polysubstituted aminocarbothiol/thiohydantoin-pyrrolidine derivatives

  • Samet Poyraz
  • Samet Belveren
  • Mahmut Ülger
  • Ertan Şahin
  • H. Ali DöndaşEmail author
Original Paper

Abstract

A series of novel functionalized polysubstituted aminocarbothiol/thiohydantoin-pyrrolidine derivatives were prepared from amino acid esters and aldehyde via cascade aldimine-azomethine ylide-1,3-dipolar cycloaddition and condensation reaction with benzoyl isothiocyanates afforded the corresponding aminocarbothiol pyrrolidines in an atom economy manner, which were conveniently converted into functionalized trisubstituted bicyclic thiohydantoins fused to pyrrolidine ring by sequential cyclization reaction under mild reaction conditions in good yield. The characterization and structural determination were made by spectral and X-ray crystal structural analysis. The crystal structure of cis-methyl (5R,6S,7aR)-7a-benzyl-5-(2,4-dimethoxyphenyl)-1-oxo-3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazole-6-carboxylate was determined as monoclinic, space group P-1 type using single X-ray crystallography. The most representative compounds were screened against M. tuberculosis H37Rv strain and showed moderate activity, compared to isoniazid and ethambutol, in the range of 62.5–125 µg/cm3.

Graphical abstract

Keywords

Amino acids Azomethine ylide 1,3-Dipolar cycloaddition Cyclization Heterocycles Antimycobacterial H37Rv strain 

Notes

Acknowledgements

We are grateful for support from Mersin University (Project no. BAP-SBE TEB(SP) 2014-4 YL and BAP 2015- AP2-1342.

References

  1. 1.
    Naidu KM, Nagesh HN, Singh M, Sriram D, Yogeeswari P, Sekhar KVGC (2015) Eur J Med Chem 92:415CrossRefGoogle Scholar
  2. 2.
    Danac R, Maternah CMA, Shova S, Daniloaia T, Balan M, Mangalagiu II (2015) Bioorg Med Chem 23:2318CrossRefGoogle Scholar
  3. 3.
    Gonzalo X, Casali N, Broda A, Pardieu C, Drobniewski F (2015) Int J Antimicrob Agents 45:406CrossRefGoogle Scholar
  4. 4.
    Smit B, Pavlovic RZ, Mihailovic AR, Dosen A, Curcic MG, Seklic DS, Zıvanovic MZ (2013) J Serb Chem Soc 78:217CrossRefGoogle Scholar
  5. 5.
    Arani NM, Safari J (2011) Ultrason Sonochem 18:640CrossRefGoogle Scholar
  6. 6.
    Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J (2010) J Med Chem 53:2779CrossRefGoogle Scholar
  7. 7.
    Blanc M, Cussac M, Boucherle A, Leclerc G (1992) Eur J Med Chem 27:267CrossRefGoogle Scholar
  8. 8.
    Tachibana K, Imaoka I, Shiraishi T, Yoshino H, Nakamura M, Ohta M, Kawata H, Taniguchi K, Ishikura N, Tsunenari T, Saito H, Nagamuta M, Nakagawa T, Takanashi K, Onuma E, Sato H (2008) Chem Pharm Bull 56:1555CrossRefGoogle Scholar
  9. 9.
    Froelich E, Fruehan A, Jackman M, Kirchner FK, Alexander EJ, Archer S (1954) J Am Chem Soc 76:3099CrossRefGoogle Scholar
  10. 10.
    Archer S, Unser MJ, Froelich E (1956) J Am Chem Soc 78:6182CrossRefGoogle Scholar
  11. 11.
    Kiec-Kononowicz K, Szymanska E (2002) Il Farmaco 57:909CrossRefGoogle Scholar
  12. 12.
    Eller K, Henkes E, Rossbacher R, Hoke H (2012) Amines Aliphatic. Ulmann’s Encycl Ind Chem 2:647Google Scholar
  13. 13.
    Bai XG, Yu DK, Wang JX, Zang H, He HW, Shao RG, Li XM, Wang YC (2012) Bioorg Med Chem Lett 22:6947CrossRefGoogle Scholar
  14. 14.
    Futatsugi K, Mascitti V, Guimaraes CRW, Morishita N, Cai C, DeNinno MP, Gao H, Hamilton MD, Hank R, Harris AR, Kung DW, Lavergne SY, Lefker BA, Lopaze MG, McClure KF, Munchhoff MJ, Preville C, Robinson RP, Wright SW, Bonin PD, Cornelius P, Chen Y, Kalgutkar AS (2013) Bioorg Med Chem Lett 23:194CrossRefGoogle Scholar
  15. 15.
    Bhowmik S, Kumar AKS, Batra S (2013) Tetrahedron Lett 54:2251CrossRefGoogle Scholar
  16. 16.
    Clark VM, Johnson AW, Sutherland IO, Todd A (1958) J Chem Soc 3283. doi: 10.1039/jr9580003283
  17. 17.
    Petersen U, Schenke T, Krebs A, Grohe K, Schriewer M, Haller I, Metzger KG, Endermann R, Zeiler HJ (1997) 7-(1-pyrrolidinyl)-3-quinolone- and -naphthyridone-carboxylic acid derivatives as antibacterial agents and feed additives. US Patent 5,607,942, Mar 04, 1997; (2002) Chem Abstr 138:14019Google Scholar
  18. 18.
    Pellegrino S, Clerici F, Contini A, Leone S, Pilati T, Luisa Gelmi M (2009) Tetrahedron 65:1995CrossRefGoogle Scholar
  19. 19.
    Pearson WH (1988) In: Rahman A (ed) Studies in natural products chemistry, vol 1. Elsevier, Amsterdam, p 323Google Scholar
  20. 20.
    Vidadala SR, Golz C, Strohmann C, Daniliuc CG, Waldmann H (2015) Angew Chem Int Ed 54:651Google Scholar
  21. 21.
    Forstall GJ, Knapp CC, Washington JA (1991) Antimicrob Agents Chemother 35:1679CrossRefGoogle Scholar
  22. 22.
    Schwartz RE, Liesch J, Hensens O, Zitano L, Honeycutt S, Garrity G, Fromtling RA, Onishi J, Monaghan R (1988) J Antibiot (Tokyo) 41:1774CrossRefGoogle Scholar
  23. 23.
    Johnson JH, Phillipson DW, Kahle AD (1989) J Antibiot (Tokyo) 42:1184CrossRefGoogle Scholar
  24. 24.
    Nájera C, Sansano JM (2009) Org Biomol Chem 7:4567CrossRefGoogle Scholar
  25. 25.
    Welter A, Dardenne G, Marlier M, Casimir J (1976) Phytochemistry 25:747CrossRefGoogle Scholar
  26. 26.
    He FS, Zhu H, Wang Z, Gao M, Yu XX, Deng WP (2015) Org Lett 17:4988CrossRefGoogle Scholar
  27. 27.
    Ugarriza I, Uría U, Reyes E, Carrillo L, Vicario JL (2015) Asymmetric Catal 2:26Google Scholar
  28. 28.
    Dondas HA, Sonmez S (2003) Heterocyl Commun 9:23Google Scholar
  29. 29.
    Nural Y, Dondas HA, Grigg R, Şahin E (2011) Heterocycles 83:2091CrossRefGoogle Scholar
  30. 30.
    Dondas HA, Nural Y, Duran N, Kilner C (2006) Turk J Chem 30:573Google Scholar
  31. 31.
    Nural Y, Kilincarslan R, Dondas HA, Cetinkaya B, Serin MS, Grigg R, Ince T, Kilner C (2009) Polyhedron 28:2847CrossRefGoogle Scholar
  32. 32.
    Dondas HA, Grigg R, Thornton- Pett M (1996) Tetrahedron 52:13455CrossRefGoogle Scholar
  33. 33.
    Dondas HA, Grigg R, Maclachton WS, Macperson DT, Markandu J, Sridharan V, Suganthan S (2000) Tetrahedron Lett 41:967CrossRefGoogle Scholar
  34. 34.
    Dondas HA, Grigg R, Kilner C (2003) Tetrahedron 59:8481CrossRefGoogle Scholar
  35. 35.
    Dondas HA, Fiswick CWG, Grigg R, Kilner C (2004) Tetrahedron 60:3473CrossRefGoogle Scholar
  36. 36.
    Dondas HA, Dürüst Y, Grigg R, Slater MJ, Sarker MAB (2005) Tetrahedron 61:10667CrossRefGoogle Scholar
  37. 37.
    Grigg R, Kilner C, Sarkar MAB, De la Cierva CO, Dondas HA (2008) Tetrahedron 64:8974CrossRefGoogle Scholar
  38. 38.
    Dondas HA, Retamosa MG, Sansano JM (2017) Synthesis 49:2819CrossRefGoogle Scholar
  39. 39.
    Nájera C, Sansano JM (2014) Curr Top Med Chem 14:1Google Scholar
  40. 40.
    Nájera C, Sansano JM, Yus M (2015) Org Biomol Chem 13:8596CrossRefGoogle Scholar
  41. 41.
    Yoo EJ (2015) Synlett 26:2189CrossRefGoogle Scholar
  42. 42.
    Pavlovska TL, Redkin RG, Lipson VV, Atamanuk DV (2016) Mol Divers 20:299CrossRefGoogle Scholar
  43. 43.
    Palomino JC, Portaels F (1999) Eur J Clin Microbiol Infect Dis 18:380CrossRefGoogle Scholar
  44. 44.
    Rigaku/MSC (2005) CrystalClear. Rigaku/MSC Inc., The Woodlands, TexasGoogle Scholar
  45. 45.
    Sheldrick GM (1997) SHELXS97 and SHELXL97. University of Göttingen, GermanyGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  1. 1.Department of Chemistry, Faculty of PharmacyMersin UniversityMersinTurkey
  2. 2.Department of Pharmaceutical Microbiology, Faculty of PharmacyMersin UniversityMersinTurkey
  3. 3.Department of Chemistry, Faculty of ScienceAtatürk UniversityErzurumTurkey

Personalised recommendations