*Result*: Alkyl sulfones: discovery of novel structural types with differentiated opportunities for insect control.
Title:
Alkyl sulfones: discovery of novel structural types with differentiated opportunities for insect control.
Authors:
Edmunds AJF; Syngenta Crop Protection AG, Stein, Switzerland., Muehlebach M; Syngenta Crop Protection AG, Stein, Switzerland., Jung PM; Syngenta Crop Protection AG, Stein, Switzerland., Hueter OF; Syngenta Crop Protection AG, Stein, Switzerland., Stoller A; Syngenta Crop Protection AG, Stein, Switzerland., Jeanguenat A; Syngenta Crop Protection AG, Stein, Switzerland., Emery D; Syngenta Crop Protection AG, Stein, Switzerland., Sikervar V; Jealott's Hill International Research Centre, Bracknell, UK., Sen I; Syngenta Biosciences Pvt Ltd, Corlim, India., Rendler S; Syngenta Crop Protection AG, Stein, Switzerland., Buchholz A; Syngenta Crop Protection AG, Stein, Switzerland.
Source:
Pest management science [Pest Manag Sci] 2025 May; Vol. 81 (5), pp. 2491-2510. Date of Electronic Publication: 2024 Jul 18.
Publication Type:
Journal Article; Review
Language:
English
Journal Info:
Publisher: Published for SCI by Wiley Country of Publication: England NLM ID: 100898744 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1526-4998 (Electronic) Linking ISSN: 1526498X NLM ISO Abbreviation: Pest Manag Sci Subsets: MEDLINE
Imprint Name(s):
Original Publication: West Sussex, UK : Published for SCI by Wiley, c2000-
MeSH Terms:
References:
Yoshihiko N, Masaki T, Mai I, Yoshihiko N, Masaki T, Hiroji Y et al., Discovery of oxazosulfyl: A novel broad‐spectrum insecticide, in Recent Highlights in the Discovery and Optimization of Crop Protection Products, Academic Press, Cambridge, Massachusetts, pp. 261–267 (2021).
Suzuki T and Yamato S, Oxazosulfyl, a novel sulfyl insecticide, binds to and stabilizes the voltage‐gated sodium channels in the slow‐inactivated state. J Agric Food Chem 69:4048–4055 (2021).
Goodchild J, Chen Y‐J, Blythe J, Firth LC, Hirst E, Bess K et al., A novel class of insecticidal alkyl sulfones are potent inhibitors of vesicular acetylcholine transport. Pestic Biochem Phys 201:105854 (2024).
Sluder A, Shah S, Cassayre J, Clover R and Maienfisch P, Spiroindolines identify the vesicular acetylcholine transporter as a novel target for insecticide action. PLoS One 7:e34712 (2012).
Edmunds AJF, Muehlebach M, Stoller A, Loiseleur O, Buchholz A, Hueter OF et al., Pesticidally active bi‐ or tricyclic heterocycles with sulfur containing substituents WO2015000715 (2015).
Lamberth C, Agrochemical lead optimization by scaffold hopping. Pest Manag Sci 74:282–292 (2018).
Takyo H, Takahashi M, Tanabe T, Nokura Y, Ito M, Iwata A et al., Fused heterocyclic compound and use for pest control thereof WO2012086848 (2012).
Béchamp A, De l'action des protosels de fer sur la nitronaphtaline et la nitrobenzine. nouvelle méthode de formation des bases organiques artificielles de Zinin. Annales de chimie et de physique 42:186–196 (1854).
Jung PM, Edmunds AJF, Jeanguenat A and Muehlebach M, Pesticidally active heterocyclic derivatives with sulfur containing substituents WO2016058928 (2016).
Bessard Y and Crettaz R, The preparation of pyridinecarboxylates from chloropyridine by the palladium‐catalyzed alkoxycarbonylation. Heterocycles 51:2589–2602 (1999).
Takahashi M, Ito M, Nokura Y, Tanabe T and Shimizu C, Fused Heterocyclic Compounds WO2013191113 (2013).
Kumar A, Bagdi M, Sougata R, Majee SA and Hajra A, Copper‐catalyzed synthesis of Imidazo[1,2‐a]pyridines through tandem imine formation‐oxidative cyclization under ambient air: one‐step synthesis of Zolimidine on a gram‐scale. Adv Synth Catal 355:1741–1747 (2013).
Rivara S, Piersanti G, Bartoccini F, Diamantini G, Pala D, Riccioni T et al., Minetti P synthesis of (E)‐8‐(3‐Chlorostyryl)caffeine analogues leading to 9‐deazaxanthine derivatives as dual A2A antagonists/MAO‐B inhibitors. J Med Chem 56:1247–1261 (2013).
(a) Jung PMJ, Edmunds A, Jeanguenat A, Muehlebach M, Stoller A, Emery D et al., Preparation of pesticidally active heterocyclic derivatives with sulphur containing substituents WO2016/023954 (2016).
(b) Jung PMJ, Edmunds A, Muehlebach M and Hall RG, Preparation of pesticidally active heterocyclic derivatives with sulphur and cyclopropyl containing substituents WO2017089190 (2017).
(a) Gerus II, Tolmachova NA, Vdovenko SI, Froehlich R and Haufe G, A convenient synthesis and chemical properties of 3‐acylamino‐6‐polyfluoroalkyl‐2H‐pyran‐2‐ones. Synthesis 8:1269–1278 (2005).
(b) Tolmachova NA, Dolovanyuk VG, Gerus II, Kondratov IS, Polovinko VV and Bergander K, Haufe G catalytic hydrogenation of 3‐amino‐ 6‐(trifluoromethyl)‐5,6‐dihydropyridin‐2(1H)‐ones and its use in the synthesis of trifluoromethyl‐containing mimetics of ornithine and thalidomide. Synthesis 7:1149–1156 (2011).
Hall RG, Goegh T, Jung PMJ, Edmunds A, Jeanguenat A, Muehlebach M et al., Pesticidally active heterocyclic derivatives with sulphur containing substituents WO2016/020286 (2016).
Muehlebach M, Jung PMJ, Edmunds A, Sikervar V, Rawal G, Sen I, Hall, R G, Pesticidally Active Heterocyclic Derivatives with Sulphur Containing Substituents WO2017/134066 (2017).
Morice C and Wermuth CG, Ring transformations, in The Practice of Medicinal Chemistry, 4th edn, ed. by Wermuth CG, Aldous D, Raboisson P and Rognan D. Academic Press, London, pp. 243–266 (2015).
Joule JA and Mills K, Heterocyclic Chemistry, 5th edn. Wiley‐Blackwell, Hoboken (2010).
Liverton NJ, Butcher JW, Claibourne CF, Claremon DA, Libby BE, Nguyen KT et al., Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen‐activated protein kinase. J Med Chem 42:2180–2190 (1999).
Muehlebach M, Titulaer R, Emery D, Edmunds A, Stoller A, Jung PM et al., Preparation of pesticidally active imidazole derivatives with sulphur containing substituents WO 2015/144895 (2015).
Voss ME, Beer CM, Mitchell SA, Blomgren PA and Zhichkin PE, A simple and convenient one‐pot method for the preparation of heteroaryl‐2‐imidazoles from nitriles. Tetrahedron 64:645–651 (2008).
Holden KG, Mattson MN, Cha KH and Rapoport H, Synthesis of chiral pilocarpine analogues via a C‐8 ketone intermediate. J Org Chem 67:5913–5918 (2002).
Chen K, Peterson R, Math SK, LaMunyon JB, Testa CA and Cefalo DR, Lithium trihydroxy/triisopropoxy‐2‐pyridylborate salts (LTBS): synthesis, isolation, and use in modified Suzuki‐Miyaura cross‐coupling reactions. Tetrahedron Lett 53:4873–4876 (2012).
Cook XAF, de Gombert A, McKnight J, Pantaine LRE and Willis MC, The 2‐pyridyl problem: challenging nucleophiles in cross‐coupling arylations. Angew Chem Int Ed 60:11068–11091 (2021).
Muehlebach M, Titulaer R, Emery D, Edmunds A, Stoller A, Jung PM et al., Preparation of 1,2,4‐triazole derivatives with sulphur containing substituents as pesticides such as insecticides WO 2015/144826 (2015).
Bonanomi G, Braggio S, Capelli AM, Checchia A, Di Fabio R, Marchioro C et al., Triazolyl azabicyclo[3.1.0]hexanes: a class of potent and selective dopamine D3 receptor antagonists. ChemMedChem 5:705–715 (2010).
Edmunds A, Jung PM, Muehlebach M, Jeanguenat A, Emery D, Hall RG et al., Preparation of pesticidally active heterocyclic derivatives with sulphur containing substituents. WO 2017/055147 (2017).
Muehlebach M, Edmunds A, Stoller A, Miller NA and Hueter OF, Preparation of Pesticidally Active Substituted 5,5‐Bicyclic Heterocycles with Sulphur Containing Substituents WO2015/091945 (2015).
Jung PM, Hueter OF, Edmunds A, Muehlebach M, Cassayre JY, Hall RG et al., Pesticidally active tetracyclic derivatives with sulfur containing substituents WO2016091731 (2016).
Sikervar V, Sen I, Emery D, Muehlebach M, Rendler S, Stoller A et al., Pesticidally active heterocyclic derivatives with sulfur containing substituents. WO 2020174094 (2020).
Stoller A, Jeanguenat A, Edmunds A, Jung PMJ, Emery D, Muehlebach M et al., Preparation of Pesticidally Active Heterocyclic Derivatives with Sulfur Containing Substituents WO2016/005263 (2016).
Buchholz A and Trapp S, How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries. Pest Manag Sci 72:929–939 (2016).
Buchholz A, O'Sullivan AC and Trapp S, What makes a good compound against sucking pests? in Discovery and Synthesis of Crop Protection Products, American Chemical Society: Washington, DC, pp. 93–109 (2015).
Suzuki T and Yamato S, Oxazosulfyl, a novel sulfyl insecticide, binds to and stabilizes the voltage‐gated sodium channels in the slow‐inactivated state. J Agric Food Chem 69:4048–4055 (2021).
Goodchild J, Chen Y‐J, Blythe J, Firth LC, Hirst E, Bess K et al., A novel class of insecticidal alkyl sulfones are potent inhibitors of vesicular acetylcholine transport. Pestic Biochem Phys 201:105854 (2024).
Sluder A, Shah S, Cassayre J, Clover R and Maienfisch P, Spiroindolines identify the vesicular acetylcholine transporter as a novel target for insecticide action. PLoS One 7:e34712 (2012).
Edmunds AJF, Muehlebach M, Stoller A, Loiseleur O, Buchholz A, Hueter OF et al., Pesticidally active bi‐ or tricyclic heterocycles with sulfur containing substituents WO2015000715 (2015).
Lamberth C, Agrochemical lead optimization by scaffold hopping. Pest Manag Sci 74:282–292 (2018).
Takyo H, Takahashi M, Tanabe T, Nokura Y, Ito M, Iwata A et al., Fused heterocyclic compound and use for pest control thereof WO2012086848 (2012).
Béchamp A, De l'action des protosels de fer sur la nitronaphtaline et la nitrobenzine. nouvelle méthode de formation des bases organiques artificielles de Zinin. Annales de chimie et de physique 42:186–196 (1854).
Jung PM, Edmunds AJF, Jeanguenat A and Muehlebach M, Pesticidally active heterocyclic derivatives with sulfur containing substituents WO2016058928 (2016).
Bessard Y and Crettaz R, The preparation of pyridinecarboxylates from chloropyridine by the palladium‐catalyzed alkoxycarbonylation. Heterocycles 51:2589–2602 (1999).
Takahashi M, Ito M, Nokura Y, Tanabe T and Shimizu C, Fused Heterocyclic Compounds WO2013191113 (2013).
Kumar A, Bagdi M, Sougata R, Majee SA and Hajra A, Copper‐catalyzed synthesis of Imidazo[1,2‐a]pyridines through tandem imine formation‐oxidative cyclization under ambient air: one‐step synthesis of Zolimidine on a gram‐scale. Adv Synth Catal 355:1741–1747 (2013).
Rivara S, Piersanti G, Bartoccini F, Diamantini G, Pala D, Riccioni T et al., Minetti P synthesis of (E)‐8‐(3‐Chlorostyryl)caffeine analogues leading to 9‐deazaxanthine derivatives as dual A2A antagonists/MAO‐B inhibitors. J Med Chem 56:1247–1261 (2013).
(a) Jung PMJ, Edmunds A, Jeanguenat A, Muehlebach M, Stoller A, Emery D et al., Preparation of pesticidally active heterocyclic derivatives with sulphur containing substituents WO2016/023954 (2016).
(b) Jung PMJ, Edmunds A, Muehlebach M and Hall RG, Preparation of pesticidally active heterocyclic derivatives with sulphur and cyclopropyl containing substituents WO2017089190 (2017).
(a) Gerus II, Tolmachova NA, Vdovenko SI, Froehlich R and Haufe G, A convenient synthesis and chemical properties of 3‐acylamino‐6‐polyfluoroalkyl‐2H‐pyran‐2‐ones. Synthesis 8:1269–1278 (2005).
(b) Tolmachova NA, Dolovanyuk VG, Gerus II, Kondratov IS, Polovinko VV and Bergander K, Haufe G catalytic hydrogenation of 3‐amino‐ 6‐(trifluoromethyl)‐5,6‐dihydropyridin‐2(1H)‐ones and its use in the synthesis of trifluoromethyl‐containing mimetics of ornithine and thalidomide. Synthesis 7:1149–1156 (2011).
Hall RG, Goegh T, Jung PMJ, Edmunds A, Jeanguenat A, Muehlebach M et al., Pesticidally active heterocyclic derivatives with sulphur containing substituents WO2016/020286 (2016).
Muehlebach M, Jung PMJ, Edmunds A, Sikervar V, Rawal G, Sen I, Hall, R G, Pesticidally Active Heterocyclic Derivatives with Sulphur Containing Substituents WO2017/134066 (2017).
Morice C and Wermuth CG, Ring transformations, in The Practice of Medicinal Chemistry, 4th edn, ed. by Wermuth CG, Aldous D, Raboisson P and Rognan D. Academic Press, London, pp. 243–266 (2015).
Joule JA and Mills K, Heterocyclic Chemistry, 5th edn. Wiley‐Blackwell, Hoboken (2010).
Liverton NJ, Butcher JW, Claibourne CF, Claremon DA, Libby BE, Nguyen KT et al., Design and synthesis of potent, selective, and orally bioavailable tetrasubstituted imidazole inhibitors of p38 mitogen‐activated protein kinase. J Med Chem 42:2180–2190 (1999).
Muehlebach M, Titulaer R, Emery D, Edmunds A, Stoller A, Jung PM et al., Preparation of pesticidally active imidazole derivatives with sulphur containing substituents WO 2015/144895 (2015).
Voss ME, Beer CM, Mitchell SA, Blomgren PA and Zhichkin PE, A simple and convenient one‐pot method for the preparation of heteroaryl‐2‐imidazoles from nitriles. Tetrahedron 64:645–651 (2008).
Holden KG, Mattson MN, Cha KH and Rapoport H, Synthesis of chiral pilocarpine analogues via a C‐8 ketone intermediate. J Org Chem 67:5913–5918 (2002).
Chen K, Peterson R, Math SK, LaMunyon JB, Testa CA and Cefalo DR, Lithium trihydroxy/triisopropoxy‐2‐pyridylborate salts (LTBS): synthesis, isolation, and use in modified Suzuki‐Miyaura cross‐coupling reactions. Tetrahedron Lett 53:4873–4876 (2012).
Cook XAF, de Gombert A, McKnight J, Pantaine LRE and Willis MC, The 2‐pyridyl problem: challenging nucleophiles in cross‐coupling arylations. Angew Chem Int Ed 60:11068–11091 (2021).
Muehlebach M, Titulaer R, Emery D, Edmunds A, Stoller A, Jung PM et al., Preparation of 1,2,4‐triazole derivatives with sulphur containing substituents as pesticides such as insecticides WO 2015/144826 (2015).
Bonanomi G, Braggio S, Capelli AM, Checchia A, Di Fabio R, Marchioro C et al., Triazolyl azabicyclo[3.1.0]hexanes: a class of potent and selective dopamine D3 receptor antagonists. ChemMedChem 5:705–715 (2010).
Edmunds A, Jung PM, Muehlebach M, Jeanguenat A, Emery D, Hall RG et al., Preparation of pesticidally active heterocyclic derivatives with sulphur containing substituents. WO 2017/055147 (2017).
Muehlebach M, Edmunds A, Stoller A, Miller NA and Hueter OF, Preparation of Pesticidally Active Substituted 5,5‐Bicyclic Heterocycles with Sulphur Containing Substituents WO2015/091945 (2015).
Jung PM, Hueter OF, Edmunds A, Muehlebach M, Cassayre JY, Hall RG et al., Pesticidally active tetracyclic derivatives with sulfur containing substituents WO2016091731 (2016).
Sikervar V, Sen I, Emery D, Muehlebach M, Rendler S, Stoller A et al., Pesticidally active heterocyclic derivatives with sulfur containing substituents. WO 2020174094 (2020).
Stoller A, Jeanguenat A, Edmunds A, Jung PMJ, Emery D, Muehlebach M et al., Preparation of Pesticidally Active Heterocyclic Derivatives with Sulfur Containing Substituents WO2016/005263 (2016).
Buchholz A and Trapp S, How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries. Pest Manag Sci 72:929–939 (2016).
Buchholz A, O'Sullivan AC and Trapp S, What makes a good compound against sucking pests? in Discovery and Synthesis of Crop Protection Products, American Chemical Society: Washington, DC, pp. 93–109 (2015).
Contributed Indexing:
Keywords: VAChT inhibition; alkyl sulfones; insect control; physical chemistry; synthesis
Substance Nomenclature:
0 (Sulfones)
0 (Insecticides)
0 (Insecticides)
Entry Date(s):
Date Created: 20240718 Date Completed: 20250409 Latest Revision: 20250409
Update Code:
20260130
DOI:
10.1002/ps.8320
PMID:
39023381
Database:
MEDLINE
*Further Information*
*The discovery of novel chemical classes with novel modes of action for insect control form the backbone of innovation with the goal to deliver much-needed solutions into the hands of growers. Over the last decade, alkyl sulfones have emerged as one of the most versatile new classes and are under intensive investigation in many R&D programs in the industry, with Sumitomo Chemicals recently introducing oxazosulfyl as a first active ingredient to the market. In this review, we discuss some of our strategies to invent novel classes based upon ligand-based design, and also show how incorporation of physical chemical properties into our design enabled us to predictably control chewing and sucking pests. © 2024 Society of Chemical Industry.
(© 2024 Society of Chemical Industry.)*