Combinatorial Synthesis of Novel 9R-Acyloxyquinine Derivatives as Insecticidal Agents

Author(s): Zhiping Che*, Jinming Yang, Di Sun, Yuee Tian, Shengming Liu, Xiaomin Lin, Jia Jiang, Genqiang Chen

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 2 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: It is one of the effective ways for pesticide innovation to develop new insecticides from natural products as lead compounds. Quinine, the main alkaloid in the bark of cinchona tree as well as in plants in the same genus, is recognized as a safe and potent botanical insecticide to many insects. The structural modification of quinine into 9R-acyloxyquinine derivatives is a potential approach for the development of novel insecticides, which showed more toxicity than quinine. However, there are no reports on the insecticidal activity of 9Racyloxyquinine derivatives to control Mythimna separata.

Methods: Endeavor to discover biorational natural products-based insecticides, 20 novel 9Racyloxyquinine derivatives were prepared and assessed for their insecticidal activity against M. separata in vivo by the leaf-dipping method at 1 mg/mL.

Results: Among all the compounds, especially derivatives 5i, 5k and 5t exhibited the best insecticidal activity with final mortality rates of 50.0%, 57.1%, and 53.6%, respectively.

Conclusion: Overall, a free 9-hydroxyl group is not a prerequisite for insecticidal activity and C9- substitution is well tolerated; modification of out-ring double-bond is acceptable, and hydrogenation of double-bond enhances insecticidal activity; Quinine ring is essential and open of it is not acceptable. These preliminary results will pave the way for further modification of quinine in the development of potential new insecticides.

Keywords: Quinine, combinatorial synthesis, acyloxy, structural modification, insecticidal activity, natural products.

[1]
Scoble, M.J. The Lepidoptera: Form; Function And Diversity: Oxford, 1995, pp. 4-5.
[2]
Sharma, H.C.; Sullivan, D.J.; Bhatnagar, V.S. Population dynamics and natural mortality factors of the oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae), in South-Central India. Crop Prot., 2002, 21, 721-732.
[http://dx.doi.org/10.1016/S0261-2194(02)00029-7]
[3]
Zhang, Z.; Zhang, Y.H.; Wang, J.; Liu, J.; Tang, Q.B.; Li, X.R.; Cheng, D.F.; Zhu, X. Analysis on the migration of first-generation Mythimna separata (Walker) in China in 2013. J. Integr. Agric., 2018, 17, 1527-1537.
[http://dx.doi.org/10.1016/S2095-3119(17)61885-9]
[4]
Jiang, X.; Luo, L.; Zhang, L.; Sappington, T.W.; Hu, Y. Regulation of migration in Mythimna separata (Walker) in China: a review integrating environmental, physiological, hormonal, genetic, and molecular factors. Environ. Entomol., 2011, 40(3), 516-533.
[http://dx.doi.org/10.1603/EN10199] [PMID: 22251629]
[5]
Zeng, J.; Jiang, Y.; Liu, J. Analysis of the armyworm outbreak in 2012 and suggestions of monitoring and forecasting. Plant Prot, 2013, 39, 117-121.
[6]
Heckel, D.G. Ecology. Insecticide resistance after Silent spring. Science, 2012, 337(6102), 1612-1614.
[http://dx.doi.org/10.1126/science.1226994] [PMID: 23019637]
[7]
Isman, M.B. Botanical insecticides: a global perspective. ACS Symp. Ser., 2014, 1172, 21-30.
[http://dx.doi.org/10.1021/bk-2014-1172.ch002]
[8]
Isman, M.B. Botanical insecticides, deterrents, and repellents in modern agriculture and an increasingly regulated world. Annu. Rev. Entomol., 2006, 51, 45-66.
[http://dx.doi.org/10.1146/annurev.ento.51.110104.151146] [PMID: 16332203]
[9]
Zhang, X.; Ma, Z.Q.; Feng, J.T.; Wu, H.; Han, L.R. Review on research and development of botanical pesticides. Zhongguo Shengwu Fangzhi Xuebao, 2015, 31, 685-698.
[10]
Dayan, F.E.; Cantrell, C.L.; Duke, S.O. Natural products in crop protection. Bioorg. Med. Chem., 2009, 17(12), 4022-4034.
[http://dx.doi.org/10.1016/j.bmc.2009.01.046] [PMID: 19216080]
[11]
Caballero-Gallardo, K.; Olivero-Verbel, J.; Stashenko, E.E. Repellent activity of essential oils and some of their individual constituents against Tribolium castaneum herbst. J. Agric. Food Chem., 2011, 59(5), 1690-1696.
[http://dx.doi.org/10.1021/jf103937p] [PMID: 21291237]
[12]
Goel, M.; Dureja, P.; Rani, A.; Uniyal, P.L.; Laatsch, H. Isolation, characterization and antifungal activity of major constituents of the Himalayan lichen Parmelia reticulata Tayl. J. Agric. Food Chem., 2011, 59(6), 2299-2307.
[http://dx.doi.org/10.1021/jf1049613] [PMID: 21351753]
[13]
Lin, L.; Mulholland, N.; Wu, Q.Y.; Beattie, D.; Huang, S.W.; Irwin, D.; Clough, J.; Gu, Y.C.; Yang, G.F. Synthesis and antifungal activity of novel sclerotiorin analogues. J. Agric. Food Chem., 2012, 60(18), 4480-4491.
[http://dx.doi.org/10.1021/jf300610j] [PMID: 22439963 ]
[14]
Chen, J.T.; Su, H.J.; Huang, J.W. Isolation and identification of secondary metabolites of Clitocybe nuda responsible for inhibition of zoospore germination of Phytophthora capsici. J. Agric. Food Chem., 2012, 60(30), 7341-7344.
[http://dx.doi.org/10.1021/jf301570y] [PMID: 22738079]
[15]
Che, Z.P.; Tian, Y.E.; Yang, J.M.; Liu, S.M.; Jiang, J.; Hu, M.; Chen, G.Q. Screening of insecticidal activity of podophyllotoxin analogues against Athetis dissimilis. Nat. Prod. Commun., 2019, 14, 117-120.
[http://dx.doi.org/10.1177/1934578X1901400131]
[16]
Che, Z.P.; Yang, J.M.; Tian, Y.E.; Liu, S.M.; Jiang, J.; Chen, G.Q. Research progress in quinine compounds. Chem. Bull., 2018, 81, 792-796.
[17]
Trape, J.F. The public health impact of chloroquine resistance in Africa. Am. J. Trop. Med. Hyg., 2001, 64(1-2)(Suppl.), 12-17.
[http://dx.doi.org/10.4269/ajtmh.2001.64.12] [PMID: 11425173]
[18]
Petersen, I.; Eastman, R.; Lanzer, M. Drug-resistant malaria: molecular mechanisms and implications for public health. FEBS Lett., 2011, 585(11), 1551-1562.
[http://dx.doi.org/10.1016/j.febslet.2011.04.042] [PMID: 21530510]
[19]
Hrycyna, C.A.; Summers, R.L.; Lehane, A.M.; Pires, M.M.; Namanja, H.; Bohn, K.; Kuriakose, J.; Ferdig, M.; Henrich, P.P.; Fidock, D.A.; Kirk, K.; Chmielewski, J.; Martin, R.E. Quinine dimers are potent inhibitors of the Plasmodium falciparum chloroquine resistance transporter and are active against quinoline-resistant P. falciparum. ACS Chem. Biol., 2014, 9(3), 722-730.
[http://dx.doi.org/10.1021/cb4008953] [PMID: 24369685]
[20]
Ding, R.; Zheng, B.; Wang, Y.; Peng, Y. A cation-directed enantioselective sulfur-mediated Michael/Mannich three-component domino reaction involving chalcones as Michael acceptors. Org. Lett., 2015, 17(17), 4128-4131.
[http://dx.doi.org/10.1021/acs.orglett.5b01833] [PMID: 26295594]
[21]
Miyaji, R.; Asano, K.; Matsubara, S. Asymmetric indoline synthesis via intramolecular aza-Michael addition mediated by bifunctional organocatalysts. Org. Lett., 2013, 15(14), 3658-3661.
[http://dx.doi.org/10.1021/ol401538b] [PMID: 23844669]
[22]
Hou, W.; Wei, Q.; Liu, G.; Chen, J.; Guo, J.; Peng, Y. Asymmetric multicomponent Sulfa-Michael/Mannich cascade reaction: synthetic access to 1,2-diamino-3-organosulfur compounds and 2-nitro allylic amines. Org. Lett., 2015, 17(19), 4870-4873.
[http://dx.doi.org/10.1021/acs.orglett.5b02423] [PMID: 26375583]
[23]
Hasılcıoğulları, D.; Tanyeli, C. Enantioselective sulfa-Michael addition reaction of methyl thioglycolate to chalcones derivatives with sterically encumbered quinine squaramide organocatalyst. Tetrahedron Lett., 2018, 59, 1414-1416.
[http://dx.doi.org/10.1016/j.tetlet.2018.02.068]
[24]
İşibol, D.; Karahan, S.; Tanyeli, C. Asymmetric organocatalytic direct Mannich reaction of acetylacetone and isatin derived ketimines: Low catalyst loading in chiral cinchona-squaramides. Tetrahedron Lett., 2018, 59, 541-545.
[http://dx.doi.org/10.1016/j.tetlet.2017.12.081]
[25]
Kanberoğlu, E.; Tanyeli, C. Enantioselective Michael addition of nitroalkanes to nitroalkenes catalyzed by chiral bifunctional quinine based squaramides. Asian J. Org. Chem., 2016, 5, 114-119.
[http://dx.doi.org/10.1002/ajoc.201500339]
[26]
Susam, D.; Tanyeli, C. Enantioselective aza-Henry reaction of t-Boc protected imines and nitroalkanes with bifunctional squaramide organocatalysts. New J. Chem., 2017, 41, 3555-3561.
[http://dx.doi.org/10.1039/C6NJ04078K]
[27]
Li, M.H.; Ji, N.; Lan, T.; He, W.; Liu, R. Construction of chiral quaternary carbon center via catalytic asymmetric aza-Henry reaction with asubstituted nitroacetates. RSC Advances, 2014, 4, 20346-20350.
[http://dx.doi.org/10.1039/C4RA01390E]
[28]
Du, T.; Du, F.; Ning, Y.; Peng, Y. Organocatalytic enantioselective 1,3-dipolar cycloadditions between Seyferth-Gilbert reagent and isatylidene malononitriles: synthesis of chiral spiro-phosphonylpyrazoline-oxindoles. Org. Lett., 2015, 17(5), 1308-1311.
[http://dx.doi.org/10.1021/acs.orglett.5b00311] [PMID: 25710384]
[29]
Cheng, Y.A.; Yu, W.Z.R.; Yeung, Y.Y. Carbamate-catalyzed enantioselective bromolactamization. Angew. Chem. Int. Ed. Engl., 2015, 54(41), 12102-12106.
[http://dx.doi.org/10.1002/anie.201504724] [PMID: 26314397]
[30]
Sharma, K.; Wolstenhulme, J.R.; Painter, P.P.; Yeo, D.; Grande-Carmona, F.; Johnston, C.P.; Tantillo, D.J.; Smith, M.D. Cation-controlled enantioselective and diastereoselective synthesis of indolines: an autoinductive phase-transfer initiated 5-endo-trig process. J. Am. Chem. Soc., 2015, 137(41), 13414-13424.
[http://dx.doi.org/10.1021/jacs.5b08834] [PMID: 26397716]
[31]
Xue, X.S.; Li, X.; Yu, A.; Yang, C.; Song, C.; Cheng, J.P. Mechanism and selectivity of bioinspired cinchona alkaloid derivatives catalyzed asymmetric olefin isomerization: a computational study. J. Am. Chem. Soc., 2013, 135(20), 7462-7473.
[http://dx.doi.org/10.1021/ja309133z] [PMID: 23638651]
[32]
Mitchell, B.K. Interactions of alkaloids with galeal chemosensory cells of colorado potato beetle. J. Chem. Ecol., 1987, 13(10), 2009-2022.
[http://dx.doi.org/10.1007/BF01041728] [PMID: 24301471]
[33]
Blades, D.; Mitchell, B.K. Effect of alkaloids on feeding by Phormia regina. Entomol. Exp. Appl., 1986, 41, 299-304.
[http://dx.doi.org/10.1111/j.1570-7458.1986.tb00541.x]
[34]
Chun, M.W.; Schoonhoven, L.M. Tarsal contact chemosensory hairs of the large white butterfly Pieris brassicae and their possible role in oviposition behaviour. Entomol. Exp. Appl., 1973, 16, 343-357.
[http://dx.doi.org/10.1111/j.1570-7458.1973.tb00283.x]
[35]
Danielson, P.B.; Gloor, S.L.; Roush, R.T.; Fogleman, J.C. Cytochrome P450-mediated resistance to isoquinoline alkaloids and susceptibility to synthetic insecticides in Drosophila. Pestic. Biochem. Physiol., 1996, 55, 172-179.
[http://dx.doi.org/10.1006/pest.1996.0046]
[36]
Xu, H.H. Insecticidal Plant and Plant Insecticide., 2000. pp. 49-50
[37]
Wiles, J.A.; Phadke, A.S.; Bradbury, B.J.; Pucci, M.J.; Thanassi, J.A.; Deshpande, M. Selenophene-containing inhibitors of type IIA bacterial topoisomerases. J. Med. Chem., 2011, 54(9), 3418-3425.
[http://dx.doi.org/10.1021/jm2002124] [PMID: 21443219]
[38]
Palacio, C.; Connon, S.J. A new class of urea-substituted cinchona alkaloids promote highly enantioselective nitroaldol reactions of trifluoromethylketones. Org. Lett., 2011, 13(6), 1298-1301.
[http://dx.doi.org/10.1021/ol103089j] [PMID: 21338077]
[39]
Yanuka, Y.; Geryes, A.; Heller, M. Stereospecific epimerization, oxidation and toxine rearrangement in cinchona alkaloids catalyzed by acetic acid. Tetrahedron, 1987, 43, 911-922.
[http://dx.doi.org/10.1016/S0040-4020(01)90029-8]
[40]
Che, Z.P.; Tian, Y.E.; Liu, S.M.; Jiang, J.; Hu, M.; Chen, G.Q. Stereoselective synthesis of 4β-acyloxypodophyllotoxin derivatives as insecticidal agents. J. Asian Nat. Prod. Res., 2019, 21(10), 1028-1041.
[http://dx.doi.org/10.1080/10286020.2018.1490275] [PMID: 29974799]
[41]
Che, Z.P.; Yang, J.M.; Shan, X.J.; Tian, Y.E.; Liu, S.M.; Lin, X.M.; Jiang, J.; Hu, M.; Chen, G.Q. Synthesis and insecticidal activity of sulfonate derivatives of sesamol against Mythimna separata in vivo. J. Asian Nat. Prod. Res., 2019, 2019, 1-11.
[http://dx.doi.org/10.1080/10286020.2019.1616289] [PMID: 31120307]
[42]
Che, Z.P.; Yu, X.; Zhi, X.Y.; Fan, L.L.; Yao, X.J.; Xu, H. Synthesis of novel 4α-(acyloxy)-2′ (2′ ,6′ )-(di)halogenopodophyllotoxin derivatives as insecticidal agents. J. Agric. Food Chem., 2013, 61, 8148-8155.
[http://dx.doi.org/10.1021/jf4025079] [PMID: 23915199]
[43]
Zhang, J.; Qu, H.; Yu, X.; Zhi, X.; Chen, H.; Xu, H. Combinatorial synthesis of a series of alkyl/alkenylacyloxy derivatives at the C-28 position of toosendanin as insecticidal agents. Comb. Chem. High Throughput Screen., 2013, 16(5), 394-399.
[http://dx.doi.org/10.2174/1386207311316050004] [PMID: 23305141]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 23
ISSUE: 2
Year: 2020
Published on: 06 April, 2020
Page: [111 - 118]
Pages: 8
DOI: 10.2174/1386207323666200120112714
Price: $65

Article Metrics

PDF: 16
HTML: 3