Synthesis, Antioxidant Activity and Theoretical Investigation of Isoxazolines Derivatives of Monoterpenoids

Author(s): Melek Gul*, Serpil Eryılmaz.

Journal Name: Letters in Organic Chemistry

Volume 16 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The 3+2 cycloaddition reactions are important to generate five-membered heterocyclic compounds as well as altering biological activity effects based on structure. In the study, we synthesized new isoxazoline derivatives of different monoterpenoids and examined the structure analysis using spectroscopical analysis methods, reveal changes in the theoretical analysis related to the biological activity. These new compounds exhibit antioxidant activities; DPPH radical scavenging, ferric reducing, metal chelating activities which are significantly higher than the related commercial monoterpenoids. Theoretical approaches on the compounds containing isoxazole moiety have been performed by the DFT/B3LYP/method, 6-31G(d,p) basis set in the ground state. The global and local chemical reactivity properties of the compounds were investigated by considering the values of electronegativity, global hardness-softness, electronic chemical potential, electrophilicity index and condensed Fukui functions, local softness and local electrophilicity index. Furthermore, total energy, FMOs energy values and the dipole moment (µ), mean polarizability (α), and first order hyperpolarizability (β) values were analysed at the theoretical level to examine the polarizability characteristics of the compounds. The antioxidant activity values of the newly synthesized compounds were compared with a finding of the computational study. The results obtained exhibited good correlation on some parameters.

Keywords: [3+2] cycloaddition, isoxazoline, DFT, global reactivity descriptors, condensed Fukui function, antioxidant activity.

[1]
(a) Fabre, C.E.; Blanc, P.J.; Goma, G. Biotechnol. Prog., 1988, 14(2), 270-274.
(b) Knasko, S.C. Chem. Senses, 1992, 17(1), 27-35.
[2]
Van Vuuren, S.F.; Viljoen, A.M. Flavour Fragr J., 2007, 22(6), 540-544.
[3]
Mattos, M.; Bernini, R.B. J. Braz. Chem. Soc., 2007, 18(5), 1068-1072.
[4]
(a) Katritzky, A.R.; Marson, C.M. Angew. Chem. Int. Ed., 1984, 23(6), 420-429.
(b) Richelson, E.; Souder, T. Life Sci., 2000, 68(1), 29-39.
[5]
(a) Zhang, Y.K.; Plattner, J.J.; Easom, E.E.; Zhou, Y.; Akama, T.; Bu, W.; White, W.H.; Defauw, J.M.; Winkle, J.R.; Balko, T.W.; Guo, S.; Xue, J.; Cao, J.; Zou, W. Bioorg. Med. Chem. Lett., 2015, 25(23), 5589-5593.
(b) Kaur, K.; Kumar, V.; Sharma, A.K.; Gupta, G.K. Eur. J. Med. Chem., 2014, 77, 121-133.
[6]
Shoop, W.L.; Hartline, E.J.; Gould, B.R.; Waddell, M.E.; McDowell, R.G.; Kinney, J.B.; Lahm, G.P.; Long, J.K.; Xu, M.; Wagerle, T.; Jones, G.S.; Dietrich, R.F.; Cordova, D.; Schroeder, M.E.; Rhoades, D.F.; Benner, E.A.; Confalone, P.N. Vet. Parasitol., 2014, 201(3-4), 179-189.
[7]
Trost, B.M.; King, S.A. J. Am. Chem. Soc., 1990, 112(1), 408-422.
[8]
(a) Hohenberg, P.; Kohn, W. Phys. Rev., 1964, 136(3B), B864-B871.
(b) Kohn, W.; Sham, L.J. Phys. Rev., 1965, 140(4A), A1133-A1138.
[9]
(a) Becke, A.D. J. Chem. Phys., 1992, 96(3), 2155-2160.
(b) Becke, A.D. Phys. Rev. A, 1988, 38(6), 3098-3100.
(c) Lee, C.; Yang, W.; Parr, R.G. Phys. Rev. B, 1988, 37(2), 785-789.
(d) Becke, A.D. J. Chem. Phys., 1993, 98(7), 5648-5652.
[10]
Eryılmaz, S.; Gül, M.; İnkaya, E.; İdil, Ö.; Özdemir, N. J. Mol. Struct., 2016, 1122, 219-233.
[11]
Koopmans, T. Physica, 1933, 1(1), 104-113.
[12]
Gázquez, J.L. Chemical Reactivity Concepts in Density Functional Theory In: Chemical Reactivity Theory. A Density Functional View. Chattaraj,; P. K. Ed.; CRC Press, Taylor & Francis Group: New York, USA,, 2009; Vol 2, pp. 9-10.
[13]
Parr, R.G.; Pearson, R.G. J. Am. Chem. Soc., 1983, 105(26), 7512-7516.
[14]
Mulliken, R.S. J. Chem. Phys., 1934, 2(11), 782-793.
[15]
(a) Pearson, R.G. J. Chem. Educ., 1968, 45(9), 581-586.
(b) Pearson, R.G. J. Chem. Educ., 1968, 45(10), 643-648.
(c) Pearson, R.G. J. Chem. Educ., 1999, 76(2), 267-270.
(d) Pearson, R.G. J. Am. Chem. Soc., 1963, 85(22), 3533-3539.
[16]
Pearson, R.G. Proc. Nat. Acad. Sci., 1986, 83(22), 8440-8441.
[17]
Parr, R.G.; Pearson, R.G. J. Am. Chem. Soc., 1983, 105(26), 7512-7516. Reed, J. L. J. Phys. Chem. A, 1997, 101(40), 7396-7400.
[18]
Pearson, R.G. Proc. Natl. Acad. Sci. USA, 1986, 83(22), 8440-8441.
[19]
(a) Parr, R.G.; Szentpaly, L.V.; Liu, S. J. Am. Chem. Soc., 1999, 121(9), 1922-1924.
(b) Chattaraj, P.K.; Roy, D.R. Chem. Rev., 2007, 107(9), PR46-PR74.
[20]
Parr, R.G.; Yang, W. J. Am. Chem. Soc., 1984, 106(14), 4049-4050.
[21]
Yang, W.; Parr, R.G.; Pucci, R. J. Chem. Phys., 1984, 81(6), 2862-2863.
[22]
Fukui, K. Pure Appl. Chem., 1982, 54(10), 1825-1836.
[23]
Ayers, P.W.; Levy, M. Theor. Chem. Acc., 2000, 103(3-4), 353-360.
[24]
Ayers, P.W.; Yang, W.; Bartolotti, L.J. Fukui Function In: Chemical Reactivity Theory. A Density Functional View; P. K. Chattaraj, Ed.; CRC Press, Taylor & Francis Group: New York. USA,, 2009; 18, pp. 255-265.
[25]
Yang, W.; Mortier, W.J. J. Am. Chem. Soc., 1986, 108(19), 5708-5711.
[26]
Chattaraj, P.K.; Maiti, B.; Sarkar, U. J. Phys. Chem. A, 2003, 107(25), 4973-4975.
[27]
Roy, D.R.; Parthasarathi, R.; Padmanabhan, J.; Sarkar, U.; Subramanian, V.; Chattaraj, P.K. J. Phys. Chem. A, 2006, 110(3), 1084-1093.
[28]
Pérez, P.; Toro-Labbé, A.; Aizman, A.; Contreras, R. J. Org. Chem., 2002, 67(14), 4747-4752.
[29]
Chamorro, E.; Chattaraj, P.K.; Fuentealba, P. J. Phys. Chem. A, 2003, 107(36), 7068-7072.
[30]
Yang, W.; Parr, R.G. Proc. Nat. Acad. Sci., 1985, 82(20), 6723-6726.
[31]
(a) Sánchez-Márquez, J.; Zorrilla, D.; Sánchez-Coronilla, A.; Desireé, M.; Navas, J.; Fernández-Lorenzo, C.; Alcantara, R.; Martín-Calleja, J. J. Mol. Model., 2014, 20(11), 2492.
[32]
Pluta, T.; Zerzucha, P. J. Comput. Methods Sci. Eng., 2004, 4(3), 345-355.
[33]
Nataraj, A.; Balachandran, V.; Karthick, T. J. Mol. Struct., 2013, 1031, 221-233.
[34]
Ramalingam, S.; Karabacak, M.; Periandy, S.; Puviarasan, N.; Tanuja, D. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2012, 96, 207-220.
[35]
(a) Gul, M.; Tutar, A. J. Heterocycl. Chem., 2014, 51(2), 327-335.
(b) Eryılmaz, S.; Gül, M.; İnkaya, E.; Taş, M. J. Mol. Struct., 2016, 1108, 209-222.
[36]
Deng, S.; Gangadharmath, U.; Chang, C.W.T. J. Org. Chem., 2006, 71(14), 5179-5185.
[37]
Pérez, P.; Domingo, L.R.; Aurell, M.J.; Contreras, R. Tetrahedron, 2003, 59(17), 3117-3125.
[38]
(a) Houk, K.N.; Sims, J.; Duke, R.E.; Strozier, R.W.; George, J.K. J. Am. Chem. Soc., 1973, 95(22), 7287-7301.
(b)Feuer, H., Ed.; Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis: Novel Strategies in Synthesis, 1st ed; John Wiley & Sons: New York, 2003.
[39]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.; Peralta, J.E.; Ogliaro, F.; Bearpark, M.; Heyd, J.J.; Brothers, E.; Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J.M.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zakrzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dapprich, S.; Daniels, A.D.; Farkas, Ö.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian, Inc., Wallingford CT , 2009.
[40]
GaussView. Version 5. Dennington, R.; Keith, T.; Millam, J. Semichem Inc. Shawnee Mission. KS. . (2009).
[41]
(a) Kamal, A.; Bharathi, E.V.; Reddy, J.S.; Ramaiah, M.J.; Dastagiri, D.; Reddy, M.K.; Viswanath, A.; Reddy, T.L.; Shaik, T.B.; Pushpavalli, S.N.C.V.L.; Bhadra, M.P. Eur. J. Med. Chem., 2011, 46(2), 691-703.
(b) Ribeiro, C.J.; Kumar, S.P.; Moreira, R.; Santos, M.M. Tetrahedron Lett., 2012, 53(3), 281-284.
(c) Kok, S.H.L.; Gambari, R.; Chui, C.H.; Yuen, M.C.W.; Lin, E.; Wong, R.S.M.; Lau, F.Y.; Cheng, G.Y.M.; Lam, W.S.; Chan, S.H.; Lam, K.H.; Cheng, C.H.; Lai, P.B.S.; Yu, M.W.Y.; Cheung, F.; Tang, J.C.O.; Chan, A.S.C. Bioorg. Med. Chem., 2008, 16(7), 3626-3631.
[42]
(a) Shah, T.; Desai, V. J. Serbian. Chem. Soc., 2007, 72(5), 443-449.
(b) Bhimwal, R.; Sharma, A.K.; Jain, A. J. Adv. Pharm. Educ. Res., 2011, 1(5), 251-258.
[43]
McHutchison, J.G.; Manns, M.P.; Muir, A.J.; Terrault, N.A.; Jacobson, I.M.; Afdhal, N.H.; Heathcate, E.J.; Zeuzem, S.; Reesink, H.W.; Garg, J.; Bsharat, M.; George, S.; Kauffman, R.S.; Adda, N.; Di Bisceglie, A.M. New. Engl. J. Med., 2010, 362(14), 1292-1303.
[44]
Ruberto, G.; Baratta, M.T. Food Chem., 2000, 69(2), 167-174.
[45]
Kamal‐Eldin, A.; Appelqvist, L.Å. Lipids, 1996, 31(7), 671-701.
[46]
Aazza, S.; Lyoussi, B.; Miguel, M.G. Molecules, 2011, 16(9), 7672-7690.
[47]
Laguerre, M.; Lecomte, J.; Villeneuve, P. Prog. Lipid Res., 2007, 46(5), 244-282.
[48]
(a) Gülçin, İ. Innovative. Food Sci. Emerg. Technol., 2010, 11(1), 210-218.
(b) Mathew, S.; Abraham, T.E. Food and Chem. Toxicol., 2006, 44(2), 198-206.
[49]
Carocho, M.; Ferreira, I.C. Food Chem. Toxicol., 2013, 51, 15-25.
[50]
Brand-Williams, W.; Cuvelier, M.E.; Berset, C.L.W.T. LWT-Food Sci. Technol., 1995, 28(1), 25-30.
[51]
Benzie, I.F. J.J. Strain Anal. Biochem., 1996, 239(1), 70-76.
[52]
Dinis, T.C.; Madeira, V.M.; Almeida, L.M. Arch. Biochem. Biophys., 1994, 315(1), 161-169.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 6
Year: 2019
Page: [501 - 510]
Pages: 10
DOI: 10.2174/1570178616666181226154540
Price: $65

Article Metrics

PDF: 21
HTML: 2