Pydiflumetofen

Last updated
Pydiflumetofen
Pydiflumetofen.svg
Names
Preferred IUPAC name
3-(Difluoromethyl)-N-methoxy-1-methyl-N-[1-(2,4,6-trichlorophenyl)-2-propanyl]-1H-pyrazole-4-carboxamide
Other names
SYN545974
Identifiers
3D model (JSmol)
20345474
ChEBI
ChemSpider
ECHA InfoCard 100.252.186 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 817-852-1
PubChem CID
UNII
  • InChI=1S/C16H16Cl3F2N3O2/c1-8(4-10-12(18)5-9(17)6-13(10)19)24(26-3)16(25)11-7-23(2)22-14(11)15(20)21/h5-8,15H,4H2,1-3H3 Yes check.svgY
    Key: DGOAXBPOVUPPEB-UHFFFAOYSA-N Yes check.svgY
  • CC(CC1=C(C=C(C=C1Cl)Cl)Cl)N(C(=O)C2=CN(N=C2C(F)F)C)OC
Properties [1]
C16H16Cl3F2N3O2
Molar mass 426.67
AppearanceOff-white solid
Density g/cm3
Melting point 113°C
1.5 mg/L (20 °C)
log P 3.8
Hazards
GHS labelling: [2]
GHS-pictogram-silhouette.svg GHS-pictogram-pollu.svg
Warning
H351, H361f, H410
P203, P273, P280, P318, P391, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Pydiflumetofen is a broad spectrum fungicide used in agriculture to protect crops from fungal diseases. It was first marketed by Syngenta in 2016 using their brand name Miravis. The compound is an amide which combines a pyrazole acid with a substituted phenethylamine to give an inhibitor of succinate dehydrogenase, [3] an enzyme that inhibits cellular respiration in almost all living organisms. [4]

Contents

History

Inhibition of succinate dehydrogenase, the complex II in the mitochondrial respiration chain, has been known as a fungicidal mechanism of action since the first examples were marketed in the 1960s. The first compound in this class was carboxin, which had a narrow spectrum of useful biological activity, mainly on basidiomycetes and was used as a seed treatment. [5] [6] By 2016, at least 17 further examples of this mechanism of action were developed by crop protection companies, with the market leader being boscalid, owing to its broader spectrum of fungal species controlled. However, it lacked full control of important cereal diseases, especially septoria leaf blotch Zymoseptoria tritici . [5]

Pyrazole intermediate Pyrazole SDHI intermediate.svg
Pyrazole intermediate

A group of compounds which did control septoria were amides of pyrazole-4-carboxylic acid, with the most successful being derivatives with an N-methyl group and a difluromethyl group in position 3 of the ring. These include penthiopyrad and fluxapyroxad. [7] Research chemists at Syngenta made many analogues of this type [8] in the search for new products and by 2008 had discovered benzovindiflupyr, isopyrazam, sedaxane and pydiflumetofen. [5]

Synthesis

Pydiflumetofen combines 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid with a novel amine derivative which was made from 2,4,6-trichlorobenzaldehyde. [9]

Pydiflumetofen synthesis.svg

A nitrostyrene is formed in a Henry reaction between the aldehyde and nitroethane. A reduction reaction converts it to a ketone which forms an imine with methoxyamine. This, in turn, is reduced with sodium cyanoborohydride to give the amine required for amide formation with the acid chloride of the pyrazole. [9]

Mechanism of action

Succinate dehydrogenase inhibitors (SDHI) of this type act by binding at the quinone reduction site of the enzyme complex, preventing ubiquinone from doing so. As a consequence, the tricarboxylic acid cycle and electron transport chain cannot function. [10] [11] [12]

Usage

Pydiflumetofen has fungicidal effects against a wide range of crop pests. These include Alternaria , grey mould ( Botrytis cinerea ), Cercospora (leaf spot), septoria, powdery mildews (e.g. Uncinula necator ), and scab (e.g. Venturia pyrina ). As a result, it has potential use in crops including cereals, corn, soybeans, vegetables, peanut, curcubits, potato and fruit. [13] [14] [15] The compound was introduced in the US in 2018 but estimated usage that year was low at only 4,000 pounds (1,800 kg). [16] The compound is registered for use on peanut and fruits. [15] As of 2023 the compound is also registered in Argentina, Australia, Canada and New Zealand. [17]

Human safety

Pydiflumetofen has low acute toxicity: [12] : 8  the Codex Alimentarius database maintained by the FAO lists the maximum residue limits for it in various food products. [18]

Environmental effects

The compound is very persistent in field conditions and its environmental fate and consequent ecotoxicology have been reviewed. [12] : 11–15  In one laboratory study, the R enantiomer of the compound was shown to be more toxic to Zebrafish, which was interpreted to be owing to its higher potency as an SDHI inhibitor than the S isomer. [19] [20]

Resistance management

Fungal populations have the ability to develop resistance to SDHI inhibitors. [21] This potential can be mitigated by careful management. Reports of individual pest species becoming resistant [1] are monitored by manufacturers, regulatory bodies such as the EPA and the Fungicides Resistance Action Committee (FRAC). [22] The risks of resistance developing can be reduced by using a mixture of two or more fungicides which each have activity on relevant pests but with unrelated mechanisms of action. FRAC assigns fungicides into classes so as to facilitate this. [23]

Brands

Pydiflumetofen is the ISO common name [24] for the active ingredient which is formulated into the branded product sold to end-users. Miravis is the brand name for Syngenta's suspension concentrate, which it also calls Adepidyn technology. [15] [17]

Related Research Articles

<span class="mw-page-title-main">Pesticide resistance</span> Decreased effectiveness of a pesticide on a pest

Pesticide resistance describes the decreased susceptibility of a pest population to a pesticide that was previously effective at controlling the pest. Pest species evolve pesticide resistance via natural selection: the most resistant specimens survive and pass on their acquired heritable changes traits to their offspring. If a pest has resistance then that will reduce the pesticide's efficacy – efficacy and resistance are inversely related.

Fungicides are pesticides used to kill parasitic fungi or their spores. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, and profit. Fungicides are used both in agriculture and to fight fungal infections in animals. Fungicides are also used to control oomycetes, which are not taxonomically/genetically fungi, although sharing similar methods of infecting plants. Fungicides can either be contact, translaminar or systemic. Contact fungicides are not taken up into the plant tissue and protect only the plant where the spray is deposited. Translaminar fungicides redistribute the fungicide from the upper, sprayed leaf surface to the lower, unsprayed surface. Systemic fungicides are taken up and redistributed through the xylem vessels. Few fungicides move to all parts of a plant. Some are locally systemic, and some move upward. Most fungicides that can be bought retail are sold in liquid form, the active ingredient being present at 0.08% in weaker concentrates, and as high as 0.5% for more potent fungicides. Fungicides in powdered form are usually around 90% sulfur.

<span class="mw-page-title-main">Succinate dehydrogenase</span> Enzyme

Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes. It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. Histochemical analysis showing high succinate dehydrogenase in muscle demonstrates high mitochondrial content and high oxidative potential.

Pyrazole is an organic compound of azole group with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon atoms and two adjacent nitrogen atoms, which are in ortho-substitution. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugate acid 2.49 at 25 °C). Pyrazoles are also a class of compounds that have the ring C3N2 with adjacent nitrogen atoms. Notable drugs containing a pyrazole ring are celecoxib (celebrex) and the anabolic steroid stanozolol.

A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within the ring.

The cereal grain wheat is subject to numerous wheat diseases, including bacterial, viral and fungal diseases, as well as parasitic infestations.

Acibenzolar-<i>S</i>-methyl Chemical compound

Acibenzolar-S-methyl is the ISO common name for an organic compound that is used as a fungicide. Unusually, it is not directly toxic to fungi but works by inducing systemic acquired resistance, the natural defence system of plants.

<span class="mw-page-title-main">Azoxystrobin</span> Chemical compound

Azoxystrobin is a broad spectrum systemic fungicide widely used in agriculture to protect crops from fungal diseases. It was first marketed in 1996 using the brand name Amistar and by 1999 it had been registered in 48 countries on more than 50 crops. In the year 2000 it was announced that it had been granted UK Millennium product status.

<span class="mw-page-title-main">Fluxapyroxad</span> Chemical compound

Fluxapyroxad is a broad-spectrum pyrazole-carboxamide fungicide used on a large variety of commercial crops. It stunts fungus growth by inhibiting the succinate dehydrogenase (SQR) enzyme. Application of fluxapyroxad helps prevent many wilts and other fungal infections from taking hold. As with other systemic pesticides that have a long chemical half-life, there are concerns about keeping fluxapyroxad out of the groundwater, especially when combined with pyraclostrobin. There is also concern that some fungi may develop resistance to fluxapyroxad.

<span class="mw-page-title-main">Cyproconazole</span> Chemical compound

Cyproconazole is an agricultural fungicide of the class of azoles, used on cereal crops, coffee, sugar beet, fruit trees and grapes, on sod farms and golf courses and on wood as a preservative. It was introduced to the market by then Sandoz in 1994.

<span class="mw-page-title-main">Fludioxonil</span> Chemical compound

Fludioxonil is a synthetic phenylpyrrole chemical introduced by Ciba-Geigy in 1993 for use as a non-systemic fungicide. It is a structural analog of the natural fungicide pyrrolnitrin.

<span class="mw-page-title-main">Fluopyram</span> Chemical compound

Fluopyram is a fungicide and nematicide used in agriculture. It is used to control fungal diseases such as gray mold, powdery mildew, apple scab, Alternaria, Sclerotinia, and Monilinia. It is an inhibitor of succinate dehydrogenase.

<span class="mw-page-title-main">Oxycarboxin</span> Chemical compound

Oxycarboxin is an organic chemical used in agriculture to protect crops from fungal diseases. It was first marketed by Uniroyal in 1969 using their brand name Plantvax. The compound is an anilide which combines a heterocyclic acid with aniline to give an inhibitor of succinate dehydrogenase (SDHI).

<span class="mw-page-title-main">Sedaxane</span> Chemical compound

Sedaxane is a broad spectrum fungicide used as a seed treatment in agriculture to protect crops from fungal diseases. It was first marketed by Syngenta in 2011 using their brand name Vibrance. The compound is an amide which combines a pyrazole acid with an aryl amine to give an inhibitor of succinate dehydrogenase.

<span class="mw-page-title-main">Carboxin</span> Chemical compound used to kill fungi

Carboxin is a narrow-spectrum fungicide used as a seed treatment in agriculture to protect crops from fungal diseases. It was first marketed by Uniroyal in 1969 using their brand name Vitavax. The compound is an anilide which combines a heterocyclic acid with aniline to give an inhibitor of succinate dehydrogenase (SDHI).

<span class="mw-page-title-main">Fomesafen</span> PPOi herbicide

Fomesafen is the ISO common name for an organic compound used as an herbicide. It acts by inhibiting the enzyme protoporphyrinogen oxidase (PPO) which is necessary for chlorophyll synthesis. Soybeans naturally have a high tolerance to fomesafen, via metabolic disposal by glutathione S-transferase. As a result, soy is the most common crop treated with fomesafen, followed by other beans and a few other crop types. It is not safe for maize/corn or other Poaceae.

<span class="mw-page-title-main">Fluazifop</span> ACCase herbicide, fop, anti-grass

Fluazifop is the common name used by the ISO for an organic compound that is used as a selective herbicide. The active ingredient is the 2R enantiomer at its chiral centre and this material is known as fluazifop-P when used in that form. More commonly, it is sold as its butyl ester, fluazifop-P butyl with the brand name Fusilade.

<span class="mw-page-title-main">Boscalid</span> Chemical compound used to kill fungi

Boscalid is a broad spectrum fungicide used in agriculture to protect crops from fungal diseases. It was first marketed by BASF in 2002 using their brand name Endura. The compound is an biphenyl amide derived inhibitor of succinate dehydrogenase.

3-(Difluoromethyl)-1-methyl-1<i>H</i>-pyrazole-4-carboxylic acid Chemical compound

3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid is a chemical compound which is used commercially as an intermediate to seven fungicides which act by inhibition of succinate dehydrogenase (SDHI). It consists of a pyrazole ring with difluoromethyl, methyl and carboxylic acid groups attached in specific positions.

References

  1. 1 2 Pesticide Properties Database. "Pydiflumetofen". University of Hertfordshire.
  2. ↑ "GHS Classification". pubchem.ncbi.nlm.nih.gov. 2023-07-22. Retrieved 2023-07-27.
  3. ↑ Irie, Makoto (2017). "Pydiflumetofen" (PDF). FAO . Retrieved 2023-07-27.
  4. ↑ Bénit, Paule; Kahn, Agathe; Chretien, Dominique; et al. (2019). "Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells". PLOS ONE. 14 (11): e0224132. Bibcode:2019PLoSO..1424132B. doi: 10.1371/journal.pone.0224132 . PMC   6837341 . PMID   31697708.
  5. 1 2 3 Walter, Harald (2016). "Fungicidal Succinate-Dehydrogenase-Inhibiting Carboxamides". In Lamberth, Clemens; Dinges, Jürgen (eds.). Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals. Wiley. pp. 405–425. doi:10.1002/9783527693931.ch31. ISBN   978-3-527-33947-1.
  6. ↑ "History of SDHI-fungicides". frac.info. Retrieved 2023-07-26.
  7. ↑ "Pyrazolecarboxamide fungicides". BCPC . Retrieved 2023-07-27.
  8. ↑ Walter, Harald; Lamberth, Clemens; Corsi, Camilla (2018). "Synthesis of fungicidally active succinate dehydrogenase inhibitors with novel difluoromethylated heterocyclic acid moieties". Monatshefte für Chemie - Chemical Monthly. 149 (4): 791–799. doi:10.1007/s00706-017-2101-y. S2CID   103548298.
  9. 1 2 USpatent 8258169,Rajan, R; Walter, H& Stierli, D,"Pyrazole-4-N-alkoxycarboxamides as microbiocides",published 2012-09-04, assigned to Syngenta Crop Protection
  10. ↑ Oyedotun, Kayode S.; Lemire, Bernard D. (2004). "The Quaternary Structure of the Saccharomyces cerevisiae Succinate Dehydrogenase". Journal of Biological Chemistry. 279 (10): 9424–9431. doi: 10.1074/jbc.M311876200 . PMID   14672929.
  11. ↑ Avenot, Hervé F.; Michailides, Themis J. (2010). "Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi". Crop Protection. 29 (7): 643–651. Bibcode:2010CrPro..29..643A. doi:10.1016/j.cropro.2010.02.019.
  12. 1 2 3 Arena, Maria; Auteri, Domenica; Brancato, Alba; et al. (2019). "Peer review of the pesticide risk assessment of the active substance pydiflumetofen". EFSA Journal. 17 (10): e05821. doi: 10.2903/j.efsa.2019.5821 . PMC   7008818 . PMID   32626121.
  13. ↑ Huang, Xue-Ping; Luo, Jian; Li, Bei-Xing; Song, Yu-fei; Mu, Wei; Liu, Feng (2019). "Bioactivity, physiological characteristics and efficacy of the SDHI fungicide pydiflumetofen against Sclerotinia sclerotiorum". Pesticide Biochemistry and Physiology. 160: 70–78. doi:10.1016/j.pestbp.2019.06.017. PMID   31519259. S2CID   198268036.
  14. ↑ Duan, Yabing; Xiu, Qian; Li, Haoran; Li, Tao; Wang, Jianxin; Zhou, Mingguo (2019). "Pharmacological Characteristics and Control Efficacy of a Novel SDHI Fungicide Pydiflumetofen Against Sclerotinia sclerotiorum". Plant Disease. 103 (1): 77–82. doi: 10.1094/pdis-05-18-0763-re . PMID   30358507. S2CID   53022480.
  15. 1 2 3 Syngenta US (2021). "Miravis fungicide" . Retrieved 2023-07-27.
  16. ↑ US Geological Survey (2021-10-12). "Estimated Agricultural Use for pydiflumetofen, 2018" . Retrieved 2023-07-26.
  17. 1 2 "ADEPIDYN® technology". syngenta.com. Retrieved 2023-07-27.
  18. ↑ FAO / WHO. "Pydiflumetofen".
  19. ↑ Wang, Zhen; Tan, Yuting; Li, Yanhong; Duan, Jinsheng; Wu, Qiqi; Li, Rui; Shi, Haiyan; Wang, Minghua (2022). "Comprehensive study of pydiflumetofen in Danio rerio: Enantioselective insight into the toxic mechanism and fate". Environment International. 167: 107406. Bibcode:2022EnInt.16707406W. doi:10.1016/j.envint.2022.107406. PMID   35850082. S2CID   250463420.
  20. ↑ Wang, Zhen; Li, Rui; Zhang, Jing; Liu, Shiling; He, Zongzhe; Wang, Minghua (2021). "Evaluation of exploitive potential for higher bioactivity and lower residue risk enantiomer of chiral fungicide pydiflumetofen". Pest Management Science. 77 (7): 3419–3426. doi:10.1002/ps.6389. PMID   33797181. S2CID   232763150.
  21. ↑ Cosseboom, Scott; Hu, Mengjun (2021). "Identification and Characterization of Fungicide Resistance in Botrytis Populations from Small Fruit Fields in the Mid-Atlantic United States". Plant Disease. 105 (9): 2366–2373. doi: 10.1094/pdis-03-20-0487-re . PMID   33719541. S2CID   232231834.
  22. ↑ "Fungicides Resistance Action Committee website".
  23. ↑ "Search Fungicides to find FRAC Recommendations" . Retrieved 2020-09-04.
  24. ↑ "Compendium of Pesticide Common Names: Pydiflumetofen". BCPC. Retrieved 2023-07-27.

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