Oxycarboxin

Oxycarboxin
Names
	Preferred IUPAC name 6-Methyl-4,4-dioxo-N-phenyl-3,4-dihydro-2H-1,4λ6-oxathiine-5-carboxamide
	Other names Oxycarboxine; Dcmod; Oxicarboxin, Vitavax sulfone, Plantvax, Carbojet, 5,6-dihydro-2-methyl-1,4-oxathi-ine-3-carboxanilide-4,4-dioxide
Identifiers
CAS Number	5259-88-1;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:7858;
ChEMBL	ChEMBL1712057;
ChemSpider	20048;
ECHA InfoCard	100.023.697
KEGG	C10956;
PubChem CID	21330;
UNII	NPU5GBN17X;
CompTox Dashboard (EPA)	DTXSID8034792 ;
	InChI InChI=1S/C12H13NO4S/c1-9-11(18(15,16)8-7-17-9)12(14)13-10-5-3-2-4-6-10/h2-6H,7-8H2,1H3,(H,13,14) Key: AMEKQAFGQBKLKX-UHFFFAOYSA-N;
	SMILES CC1=C(S(=O)(=O)CCO1)/C(=N\c2ccccc2)/O;
Properties
Chemical formula	C12H13NO4S
Molar mass	267.30 g·mol−1
Melting point	120 °C (248 °F; 393 K)
Solubility in water	moderate
Solubility	acetone, DMF, ethanol, and methanol
Related compounds
Related compounds	Carboxin
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Oxycarboxin is an organic chemical used in agriculture to protect crops from fungal diseases. It was first marketed by Uniroyal in 1969 under the brand name Plantvax. The compound is a benzanilide analog which combines a heterocyclic acid with aniline to give an inhibitor of succinate dehydrogenase (SDHI).^[1]^[2]^[3]

Synthesis

Oxyxarboxin was first made by the oxidation of carboxin, as disclosed in patents filed by Uniroyal.^[4]

Ethyl 2-chloroacetoacetate is treated with 2-mercaptoethanol and base, followed by cyclisation and water removal under acidic conditions. The resultant ethyl ester of the 1,4-oxathiine heterocycle is then formed into an amide with aniline using standard conditions via the carboxylic acid and acid chloride. This gives carboxin in high overall yield.^[5] The synthesis is completed by treatment with 30% hydrogen peroxide in acetic acid.^[4]

Mechanism of action

Carboxin and oxycarboxin act by inhibition of succinate dehydrogenase (SDHI):^[6] they bind to 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.^[7]^[8]

Uses

Oxycarboxin is used to control rust diseases (e.g. soybean rust) at an application rate of 200–400 g/ha.^[3]^[9]

History

Oxycarboxin has been commercially available since 1969, when it was introduced under the brand name Plantvax.^[2]^[10]

References

^ 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 9783527339471.
^ ^a ^b Ackermann, Peter; Margot, Paul; Müller, Franz (2000). "Fungicides, Agricultural". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a12_085. ISBN 3527306730.
^ ^a ^b Shanmugasundaram, S.; Yeh, C.C.; Hartman, G.L.; Talekar, N.S. (1991). Vegetable Soybean Research Needs for Production and Quality Improvement (PDF). Taipei: Asian Vegetable Research and Development Center. pp. 86–87. ISBN 9789290580478. Archived from the original (PDF) on February 6, 2016. Retrieved 6 February 2016.
^ ^a ^b US patent 3402241, von Schmeling, B.; Kulka, M. & Harrison, W.A., "Control of plant fungal and bacterial diseases with 2, 3-dihydro-5-carboximido-6-methyl-1, 4-oxathiin, mono-and di-oxides", issued 1968-09-17, assigned to Uniroyal Inc
^ von Schmeling, B.; Kulka, Marshall (1966). "Systemic Fungicidal Activity of 1,4-Oxathiin Derivatives". Science. 152 (3722): 659–660. Bibcode:1966Sci...152..659V. doi:10.1126/science.152.3722.659. PMID 17779512. S2CID 27561137.
^ Gunatilleke, I. A. U. N.; Arst, H. N.; Scazzocchio, C. (1975). "Three genes determine the carboxin sensitivity of mitochondrial succinate oxidation in Aspergillus nidulans". Genetical Research. 26 (3): 297–305. doi:10.1017/S0016672300016098. PMID 178574.
^ 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.
^ 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.
^ Worthing C.R., ed. (1987). The Pesticide Manual - A World Compendium (Eighth ed.). British Crop Protection Council. p. 624. ISBN 0948404019.
^ Pesticide Properties Database (2023-06-15). "Oxycarboxin". University of Hertfordshire. Retrieved 2023-08-07.

[Walter-1] 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 9783527339471.

[Ullmann-2] Ackermann, Peter; Margot, Paul; Müller, Franz (2000). "Fungicides, Agricultural". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a12_085. ISBN 3527306730.

[SoyResearch-3] Shanmugasundaram, S.; Yeh, C.C.; Hartman, G.L.; Talekar, N.S. (1991). Vegetable Soybean Research Needs for Production and Quality Improvement (PDF). Taipei: Asian Vegetable Research and Development Center. pp. 86–87. ISBN 9789290580478. Archived from the original (PDF) on February 6, 2016. Retrieved 6 February 2016.

[US3402241-4] US patent 3402241, von Schmeling, B.; Kulka, M. & Harrison, W.A., "Control of plant fungal and bacterial diseases with 2, 3-dihydro-5-carboximido-6-methyl-1, 4-oxathiin, mono-and di-oxides", issued 1968-09-17, assigned to Uniroyal Inc

[5] von Schmeling, B.; Kulka, Marshall (1966). "Systemic Fungicidal Activity of 1,4-Oxathiin Derivatives". Science. 152 (3722): 659–660. Bibcode:1966Sci...152..659V. doi:10.1126/science.152.3722.659. PMID 17779512. S2CID 27561137.

[6] Gunatilleke, I. A. U. N.; Arst, H. N.; Scazzocchio, C. (1975). "Three genes determine the carboxin sensitivity of mitochondrial succinate oxidation in Aspergillus nidulans". Genetical Research. 26 (3): 297–305. doi:10.1017/S0016672300016098. PMID 178574.

[7] 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.

[8] 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.

[BCPC8-9] Worthing C.R., ed. (1987). The Pesticide Manual - A World Compendium (Eighth ed.). British Crop Protection Council. p. 624. ISBN 0948404019.

[10] Pesticide Properties Database (2023-06-15). "Oxycarboxin". University of Hertfordshire. Retrieved 2023-08-07.

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