TY - JOUR
AU - NISHIMURA, Keiichiro
AB - Abstract Prodrug-oriented molecular design was attempted for the potent acyclic neonicotinoid insecticide, clothianidin (1-(2-chloro-5-thiazolylmethyl)-3-methyl-2-nitroguanidine). Molecules bearing a CH2COCH2 bridge linking the 1,3-NH ends of clothianidin or their acetals would possibly be hydrolyzed, regenerating the mother compounds. This strategy was used to prepare seven acetals of clothianidin-based molecules that combined 2-chloro-5-thiazolylmethyl, 6-chloro-3-pyridylmethyl or 3-tetrahydrofurfuryl with a nitroimine, cyanoimine or nitromethylene group. The key intermediate, 1,3-diamino-2,2-dimethoxypropane, was prepared from the dihydroxyacetone dimer in four steps. A selected acetal showed a characteristic nerve-impulse pattern for neonicotinoids on an excised American cockroach ganglion, although the neuroblocking activity was fairly low. Some acetals were highly insecticidal against the pea aphid at 0.8–20 ppm 7 days after a spray treatment, this being in a contrast to their far weaker activity by injection into American cockroaches. The biological results suggest that the intrinsic insecticidal activities of the acetals are weak, but would exhibit enhanced activity if hydrolyzed in an external environment. neonicotinoid insecticide, prodrug, clothianidin, acetal, neuroblocking activity 1) Drabek, J., and Neumann, R., Proinsecticides. In “Progress in Pesticide Biochemistry and Toxicology” Vol. 5, eds. Hutson, D. H., and Roberts, T. R., Wiley, New York, pp. 35–86 (1985). 2) Kagabu, S., Molecular design of neonicotinoids: past, present and future. In “Chemistry of Crop Protection”, eds. Voss, G., and Ramos, G., Wiley-VCH, Weinheim, pp. 193–212 (2003). 3) Uneme, H., Iwanaga, K., Higuchi, N., Kando, Y., Okauchi, T., Akayama, A., and Minamida, I., Synthesis and insecticidal activity of nitroguanidine derivatives. 9th IUPAC Int. Congress on Pesticide Chemistry, London, Abstract 1, 1D-009 (1998). 4) Nauen, R., Ebbinghaus-Kintscher, U., Salgado, V. L., and Kaussmann, M., Thiamethoxam is a neonicotinoid precursor converted to clothianidin in insects and plants. Pestic. Biochem. Physiol., 76, 55–69 (2003). 5) Kayzer, H., Lee, C., and Wellmann, H., Thiamethoxam and imidacloprid bind to different sites on nicotinic receptors conserved pharmacology among aphids. 10th IUPAC International Congress on Chemistry of Crop Protection, Zurich, Abstract No. 348 (2002). 6) Smith, M. B., and March, J., “March’s Advanced Organic Chemistry” 5th ed., Wiley, New York, Chapter 1 (2001). 7) Widmer, H., Steinemann, A., and Maienfisch, P., Chemical and physical properties of thiamethoxam. 218th ACS National Meeting, New Orleans, Abstract AGRO-134 (1999). 8) Yamamoto, I., Yabuta, G., Tomizawa, M., Saito, T., Miyamoto, T., and Kagabu, S., Molecular mechanism for selective toxicity of nicotinoids and neonicotinoids. J. Pestic. Sci., 20, 33–40 (1995). 9) Kagabu, S., and Matsuno, H., Chloronicotinyl insecticides. 8. Crystal and molecular structures of imidacloprid and analogous compounds. J. Agric. Food Chem., 45, 276–281 (1997). 10) Matsuda, K., Buckingum, S. D., Kleier, D., Rauh, J. J., Grauso, M., and Sattelle, D. B., Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. Trends Pharmacol. Sci., 22, 573–580 (2001). 11) Smith, B. M., and March, J., “March’s Advanced Organic Chemistry” 5th ed., Wiley, New York, Chapter 12 (2001). 12) Hurd, C. D., and Nilson, M. E., Aliphatic nitroketones. J. Org. Chem., 20, 927–936 (1955). 13) Greene, T. W., and Wuts, P. G. M., “Protective Groups in Organic Synthesis” 3rd ed., Wiley, New York, Chapter 4 (1999). 14) Ferroni, E. L., DiTella, V., Ghanayem, N., Jeske, R., Jodlowski, C., O’Connell, M., Styrsky, J., Svoboda, R., Venkataraman, A., and Winkler, B. M., A three-step preparation of dihydroxyacetone phosphate dimethyl acetal. J. Org. Chem., 64, 4943–4945 (1999). 15) Shiokawa, K., Tsuboi, S., Kagabu, S., and Moriya, K., Heterocyclic compounds. Eur. Pat. Appl., EP 0192060 A1 (1986). 16) Kagabu, S., Nishiwaki, H., Sato, K., Hibi, M., Yamaoka, N., and Nakagawa, Y., Nicotinic acetylcholine receptor binding of imidacloprid-related diaza compounds with various ring sizes and their insecticidal activity against Musca domestica. Pest Manag. Sci., 58, 483–490 (2002). 17) Maienfisch, P., Huerlimann, H., and Haettenschwiler, J., A novel method for the preparation of N,N-disubstituted-N′-nitroguanidines, including a practical synthesis of the neonicotinoid insecticide clothianidin. Tetrahedron Lett., 41, 7187–7191 (2000). 18) Nakagawa, S., Okajima, N., Nishimura, K., Kitahaba, T., Fujita, T., and Nakajima, M., Quantitative structure-activity studies of substituted benzyl crysanthemates. 1. Correlations between symptomatic and neurophysiological activities against American cockroaches. Pestic. Biochem. Physiol., 17, 243–258 (1982). 19) Nishimura, K., Kanda, Y., Okazawa, A., and Ueno, T., Relationship between insecticidal and neurophysiological activities of imidacloprid and related compounds. Pestic. Biochem. Physiol., 50, 51–59 (1994). 20) Nishimura, K., Tanaka, M., Iwaya, K., and Kagabu, S., Relationship between insecticidal and nerve-excitatory activities of imidacloprid and its alkylated congeners at the imidazolidine NH site. Pestic. Biochem. Physiol., 62, 172–178 (1998). 21) Kiriyama, K., Iwaya, K., Kagabu, S., and Nishimura, K., Relationship between insecticidal and nerve activities of imidacloprid-related nitromethylene compounds and its N-alkyl congeners. J. Pestic. Sci., 26, 55–59 (2001). 22) Kiriyama, K., and Nishimura, K., Structural effects of dinotefuran and analogues on insecticidal and neural activities. Pest Manag. Sci., 58, 669–676 (2002). 23) Suzuki, T., and Miyamoto, J., Metabolism of tetramethrin in houseflies and rats in vitro. Pestic. Biochem. Physiol., 4, 86–97 (1974). 24) Gall, M., and Kamdar, B. V., Synthesis of aminoalkyl-substituted imidazo[1,2-a]- and imidazo[1,5-a]benzodiazepines. J. Org. Chem., 46, 1575–1585 (1981). 25) Axenrod, T., Sun, J., and Das, K. K., Synthesis and characterization of 5-substituted 1,3-diazacyclohexane derivatives. J. Org. Chem., 65, 1200–1206 (2000). 26) Cleare, M. J., and Hoeschele, J. D., Antitumor platinum compounds. Relation between structure and activity. Platinum Metals Rev., 17, 2–13 (1973). 27) Kojima, S., Funabora, M., Kawahara, N., and Iiyoshi, Y., Process for producing nitrogen heterocycle. PCT Int. Appl., WO 9204329 A1 (1992). 28) Kagabu, S., Yokoyama, K., Iwaya, K., and Tanaka, M., Imidacloprid and related compounds: structure and water solubility of N-alkyl derivatives of imidacloprid. Biosci. Biotechnol. Biochem., 62, 1216–1224 (1998). 29) Kagabu, S., Chloronicotinyl insecticides—discovery of a new application and future perspective. Rev. Toxicol., 1, 75–129 (1997). 30) Schulz-Jander, D. A., and Casida, J. E., Imidacloprid insecticide metabolism: human cyctochrome P450 isozymes differ in selectivity for imidazolidine oxidation versus nitroimine reduction. Toxic. Lett., 132, 65–70 (2002). 31) Schulz-Jander, D. A., Leimkuehler, W. M., and Casida, J. E., Neonicotinoid insecticides: reduction and cleavage of imidacloprid nitroimine substituent by liver microsomal and cytosolic enzymes. Chem. Res. Toxic., 15, 1158–1165 (2002). 32) Kagabu, S., Azuma, A., and Nishimura, K., Insecticidal and neuroblocking activities of thiacloprid and its acyclic analogues and their related cyanoguanidine derivatives. J. Pestic. Sci., 27, 267–271 (2002). 33) Kiriyama, K., Itazu, Y., Kagabu, S., and Nishimura, K., Insecticidal and neuroblocking activities of acetamiprid and related compounds. J. Pestic. Sci., 28, 8–17 (2003). 34) Kagabu, S., Kiriyama, K., Nishiwaki, H., Kumamoto, Y., Tada, T., and Nishimura, K., Asymmetric chloronicotinyl insecticide, 1-[1-(6-chloro-3-pyridyl)ethyl]-2-nitroiminoimidazolidine: preparation, resolution and biological activities toward insects and their nerve preparations. Biosci. Biotechnol. Biochem., 67, 980–988 (2003). 35) Testa, B., and Jenner, P., “Drug Metabolism: Chemical and Biochemical Aspects” Vol. 3, Dekker, New York, pp. 82–97 (1976). 36) Kagabu, S., Murata, N., Hibino, R., Hanzawa, M., and Nishimura, K., Insecticidal and neuroblocking potencies of thiamethoxam-type compounds against American cockroach (Periplaneta americana L.). J. Pestic. Sci., submitted. PDF This content is only available as a PDF. © 2005 by Japan Society for Bioscience, Biotechnology, and Agrochemistry This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) © 2005 by Japan Society for Bioscience, Biotechnology, and Agrochemistry
TI - Prodrug-Oriented Molecular Design of Neonicotinoids: Preparation of Imidacloprid-Related 5,5-Dimethoxy-1,3-diazacyclohexane Derivatives and Their Insecticidal Activity
JF - Bioscience Biotechnology and Biochemistry
DO - 10.1271/bbb.69.705
DA - 2005-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/prodrug-oriented-molecular-design-of-neonicotinoids-preparation-of-H8MTGj4GUO
SP - 705
EP - 713
VL - 69
IS - 4
DP - DeepDyve
ER -