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Articles

Vol. 2 No. 2 (2011): April – June 2011

Design and Synthesis of 1-(2-amino-1-(4-methoxyphenyl)ethyl) cyclohexanol Analogs as Potential Microbial Agents

DOI
https://doi.org/10.37285/ijddd.2.2.6
Submitted
November 28, 2024
Published
2024-12-08

Abstract

1-(2-amino-1-(4-methoxyphenyl)ethyl)cyclohexanol (1), on condensation with chloroacetyl chloride yielded 2-chloro-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamide (2), which on amination with hydrazine hydrate yielded in turn 2-hydrazinyl-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamide (3). Compound 3, on condensation with various aromatic aldehydes afforded a series of 2-(2-benzylidenehydrazinyl)-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)acetamides 4a-n, which upon dehydrative annulation in the presence of chloroacetyl chloride and triethylamine yielded 2-(3-chloro-2-oxo-4-phenylazetidin-1-ylamino)-N-(2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl) acetamides 5a-n. The synthesized compounds 4a-g and 5a-g were screened for their antibacterial activity against four microorganisms: Staphylococcus aureus (Gram positive), Bacillus subtilis (Gram positive), Pseudomonas aeruginosa (Gram negative) and Escherichia coli (Gram negative). They were found to exhibit good to moderate antibacterial activity. The antifungal activities of these compounds were also tested against three different fungal species. None of them were active against the species tested.

References

  1. [1] Southgate, R. The synthesis of natural β-lactam antibiotics. Contemp. Org. Synth. 1994, 1, 417-431; b) Morin, R. B.; Gorman, M. Chemistry and Biology of β-Lactam Antibiotics; Academic Press: New York, 1982.
  2. [2] Mata, E. G.; Fraga, M. A.; Delpiccolo, C. M. L. An Efficient, Stereoselective Solid-Phase Synthesis of β-Lactams Using Mukaiyama’s Salt for the Staudinger Reaction. J. Comb. Chem.2003, 5, 208-210.
  3. [3] Page, E. I. The Chemistry of β-Lactams; Blackie Academic and Professional: New York, 1992.
  4. [4] (a) Niccolai, D.; Trasi, L.; Thomas, R. J. The renewed challenge of antibacterial chemotherapy. Chem. Commun. 1997, 2333-2342; (b) Chu, D. T. W.; Plattner,J. I.; Katz, L. New Directions in Antibacterial Research. J. Med. Chem. 1996, 39, 3853-3874.
  5. [5] Van der Steen, F. H.; Van Koten, G. Synthesis of 3-amino-2-azetidinones: A literature survey.
  6. Tetrahedron 1991, 47, 7503-7524.
  7. [6] Durckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K. H. Recent Developments in the Field of β-Lactam Antibiotics. Angew. Chem. Int. Ed. Engl. 1985, 24, 180-202.
  8. [7] Abdulla, R. F.; Fuhr, K. H. Monocyclic antibiotic beta-lactams. J. Med. Chem. 1975, 18, 625-627.
  9. [8] Feigelson, G. B.; Curran, W. V.; Ziegler, C. B. 4-Substituted azetidinones as precursors to 2-substituted-3-carboxy carbapenem antibiotics and a method of producing them. US 5,371,215 1994.
  10. [9] Doherty, J. B.; Dorn, C. P.; Durette, P. L.; Finke, P. E.; MacCoss, M.; Mills, S. G.; Shah, S. K.;Sahoo, S. P.; Polo, S. A.; Hagmann, W. K. Substituted azetidinones as anti-inflammatory and antidegenerative agents. WO 94,10,143 1994.
  11. [10] Khalafallah, A. K.; Selim, M. A.; El-Hamd, R. M. A.; Elmaghraby, M. A.; Soleiman, H. A.;Raslan, M. A. Novel synthesis of some new fused/spiro heterocyclic compounds and their biological activity. Indian J. Chem. 1995, 34B, 1066-1070.
  12. [11] Parikh, K. A.; Oza, P. S.; Parikh, A. R. Synthesis of some new 2-azetidinones as potential antitubercular agents. Indian J. Chem. 2000, 39B, 716.
  13. [12] Vashi, B. S.; Mehta, D. S.; Shah, V. H. Synthesis and biological activity of 4-thiazolidinones, 2-azetidinones, 4-imidazolinone derivatives having thymol moiety. Indian J. Chem. 1995, 34B, 802-808.
  14. [13] Russo, F.; Romeo, G.; Santagati, N. A.; Caruso, A.; Cutuli, V.; Amore, D. Synthesis of new thienopyrimidobenzothiazoles and thienopyrimidobenzoxazoles with analgesic and anti-inflammatory properties. Eur. J. Med. Chem. 1994, 29,569- 578.
  15. [14] Katsura, Y.; Inoue, Y.; Nishino, S.; Tomoi, M.; Takasugi,H. Studies on antiulcer drugs. IV.Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzothiazoles and benzimidazoles. Chem. Pharm. Bull (Tokyo). 1992, 40, 1818-1822.
  16. [15] Kuhler, T. C.; Swanson, M.; Shcherbuchin, V.; Larsson, H.; Mellgard, B.; Sjostrom, J. E.Structure-Activity Relationship of 2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles as Anti-Helicobacter pylori Agents in Vitro and Evaluation of their in Vivo Efficacy J. Med. Chem. 1998,41, 1777-1788.
  17. [16] Baltork, I. M.; Khosropour, A. R.; Hojati, S. F. Mild and Efficient Synthesis of Benzoxazoles,Benzothiazoles, Benzimidazoles and Oxazolo[4,5-b]pyridines Catalyzed by Bi(III) Salts Under Solvent-Free Conditions. Monatshe Chem. 2007, 138, 663-667.
  18. [17] Nikolyukin, Y. A.; Gibboni, D. J. U.S. Pat 5710012, 1998.
  19. [18] British Pharmacopoeia, 2005; Vol. IV, Appendix XIV, p. A300.
  20. [19] European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).