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Cycloisomerization of acetylenic oximes and hydrazones under gold catalysis: Synthesis and cytotoxic evaluation of isoxazoles and pyrazoles

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Abstract

The synthesis of substituted isoxazoles and pyrazoles through a general cycloisomerization methodology has been reported. The capability of gold(III) chloride to promote cycloisomerization of both α, β-acetylenic oximes and α, β-acetylenic hydrazones is the centrepiece of the strategy. A range of acetylenic precursors were investigated to afford 28 examples of the products with good to excellent chemical yields. Selected compounds were screened for their cytotoxic potential towards COLO320 cancer cell lines. The IC50 values of the tested compounds were in the micromolar range, with the best compound, 5-(6-Methoxy-naphthalen-2-yl)-3-phenyl-isoxazole (3h) displaying an IC50 of 38.9 μM. For this compound, the crystal structure in complex with Aurora-A kinase was obtained which revealed details of its binding mode within the active site with a free energy of binding -9.54 kcal/mol.

An integration process for the synthesis of isoxazoles and pyrazoles was achieved by taking advantage of the gold catalyzed cycloisomerization strategy. These compounds show cytotoxic effect against COLO320 cancer cells with IC50 values ranging between 38.9 and 55.9 μM.

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References

  1. (a) Arcadi A 2008 Chem. Rev. 108 3266; (b) Hashmi A S K and Rudolph M 2008 Chem. Soc. Rev. 37 1766; (c) Zhang Y, Luo T and Yang Z 2014 Nat. Prod. Rev. 31 489; (d) Fürstner A 2014 Acc. Chem. Res. 47 925; (e) Hashmi A S K and Bührle 2010 Aldrichim. Acta. 43 27; (f) Wegner H A and Auzias M 2011 Angew. Chem. Int. Ed. 50 8236; (g) Patil N 2012 Chem. Asian. J. 7 2186; (h) Inamdar S M, Konala A and Patil N T 2014 Chem. Commun. 50 15124; (i) Bandini M 2011 Chem. Soc. Rev. 40 1358; (j) Patil N T and Singh V 2011 J. Organomet. Chem. 696 419; (k) Patil N T, Kavthe R D and Shinde V S 2012 Tetrahedron 68 8079; (l) Corma A, Leyva-Pérez A and Sabater M J 2011 Chem. Rev. 111 1657; (m) Patil N T 2013 Curr. Sci. 104 1671

  2. (a) Praveen C, Sagayaraj Y W and Perumal P T 2009 Tetrahedron Lett. 50 644; (b) Praveen C, Karthikeyan K and Perumal P T 2009 Tetrahedron 65 9244; (c) Praveen C, Kiruthiga P and Perumal P T 2009 Synlett 1990; (d) Praveen C, Jegatheesan S and Perumal P T 2009 Synlett 2795; (e) Praveen C, Kalyanasundaram A and Perumal P T 2010 Synlett 777; (f) Praveen C and Perumal P T 2011 Synlett 521; (g) Praveen C, Ayyanar A and Perumal P T 2011 Bioorg. Med. Chem. Lett. 21 4170; (h) Praveen C, Perumal P T 2016 Chin. J. Catal. 37 (DOI: 10.1016/S1872-2067(15)60994-9)

  3. (a) Teresa M V D and Melo P e 2005 Curr. Org. Chem. 9 925; (b) Fustero S, Simón-Fuentes A and Sanz-Cervera J F 2009 Org. Prep. Proc. Int. 41 253; (c) Kumar V, Kaur K, Gupta G K and Sharma A K 2013 Eur. J. Med. Chem. 69 735; (d) Michelot D and Melendez-Howell L M 2003 Mycol. Res. 107 131; (e) Regoli D and Barabé J 1980 Pharmacol. Rev. 32 1; (f) Sperry J and Wright D 2005 Curr. Opin. Drug Discovery Dev. 8 723; (g) Talley J J, Brown D L, Carter J S, Graneto M J, Koboldt C M, Masferrer J L, Perkins W E, Rogers R S, Shaffer A F, Zhang Y Y, Zweifel B S and Seibert K J 2000 J. Med. Chem. 43 775

  4. Margaretha P 2010 Science of Synthesis 1 109

    Google Scholar 

  5. (a) Deng X and Mani N S 2008 J. Org. Chem. 73 2412; (b) Meng L, Lorsbach B A, Sparks T C, Fettinger J C and Kurth M J 2010 J. Comb. Chem. 12 129; (c) Grotjahn D B, Van S, Combs D, Lev D A, Schneider C, Rideout M, Meyer C, Hernandez G and Majorado L 2002 J. Org. Chem. 67 9200

  6. (a) Alley M C, Scudiero D A, Monks A, Hursey M L, Czerwinski M J, Fine D L, Abbott J G M, Shoemaker R H and Boyd M R 1988 Cancer Res. 48 589; (b) Mossman T 1983 J. Immunol. Methods 65 55; (c) Wallace A C, Lasowski R A and Thornton J M 1995 Protein Eng. 8 127

  7. (a) Waldo J P and Larock R C 2005 Org. Lett. 7 5203; (b) Waldo J P, Mehta S, Neuenswander B, Lushington G H and Larock R C 2008 J. Comb. Chem. 10 658; (c) Waldo J P and Larock R C 2007 J. Org. Chem. 72 9643

  8. Short K M and Ziegler Jr. C B 1993 Tetrahedron Lett. 34 75

    Article  CAS  Google Scholar 

  9. (a) Balakrishnan B, Praveen C, Seshadri P R and Perumal P T 2013 Acta Cryst. E69 o597; (b) Balakrishnan B, Praveen C, Seshadri P R and Perumal P T 2011 Acta Cryst. E67 o1575

  10. Aldeco-Pérez E J, Álvarez-Toledano C, Toscano A, García-Estrada J G and Penieres-carrillo J G 2008 Tetrahedron Lett. 49 2942

  11. (a) Zora M, Kivrak A and Yazici C 2011 J. Org. Chem. 76 6726; (b) Zora M and Kivrak A 2011 J. Org. Chem. 76 9379

  12. Qian J, Liu Y, Zhu J, Jiang B and Xu Z (2011) Org. Lett. 13 4220

  13. (a) Keen N and Taylor S 2004 Nat. Rev. Cancer 4 927; (b) Prime M E, Courtney S M, Brookfield F A, Marston R W, Walker V, Warne J, Boyd A E, Kairies N A, von der Saal W, Limberg A, Georges G, Engh R A, Goller B, Rueger P and Rueth M 2011 J. Med. Chem. 54 312

  14. (a) Morris G M, Huey R, Lindstrom W, Sanner M F, Belew R K, Goodsell D S and Olson A J 2009 J. Comput. Chem. 30 2785; (b) Sanner M F 1999 J. Mol. Graphics Mod. 17 57

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Acknowledgements

C.P. gratefully acknowledges the financial support of the Department of Science & Technology (DST), India for providing INSPIRE faculty award. C.P. also thanks Dr. Vijayamohanan K. Pillai and Dr. D. Jeyakumar, CSIR-CECRI for infrastructure facilities.

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Correspondence to CHANDRASEKAR PRAVEEN.

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Supplementary Information

Docking poses of all the screened compounds and copy of IR,1H NMR,13C NMR and mass of compounds 3m and 5b are available at www.ias.ac.in/chemsci.

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JEYAVEERAN, J.C., PRAVEEN, C., ARUN, Y. et al. Cycloisomerization of acetylenic oximes and hydrazones under gold catalysis: Synthesis and cytotoxic evaluation of isoxazoles and pyrazoles. J Chem Sci 128, 73–83 (2016). https://doi.org/10.1007/s12039-015-0993-9

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