boscalid
{{Short description|Chemical compound used to kill fungi}}
{{chembox
|ImageFile = Boscalid Structural Formula V.1.svg
|PIN = 2-chloro-N-(4'-chloro[1,1'-biphenyl]-2-yl)pyridine-3-carboxamide
|OtherNames = BAS 510F, Nicobifen
|Section1 ={{Chembox Identifiers
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo= 188425-85-6
|Beilstein = 10092464
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 81822
|ChEMBL_Ref = {{ebicite|correct|EMBL}}
|ChEMBL = 1076544
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 184713
| DrugBank = DB12792
|EC_number = 606-143-0
|KEGG_Ref = {{keggcite|correct|kegg}}
|KEGG = C18547
|PubChem= 213013
|UNII = 32MS8ZRD1V
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C18H12Cl2N2O/c19-13-9-7-12(8-10-13)14-4-1-2-6-16(14)22-18(23)15-5-3-11-21-17(15)20/h1-11H,(H,22,23)/f/h22H
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = WYEMLYFITZORAB-UHFFFAOYSA-N
|SMILES = C1=CC=C(C(=C1)C2=CC=C(C=C2)Cl)NC(=O)C3=C(N=CC=C3)Cl
}}
|Section2={{Chembox Properties
|C=18 |H=12 |Cl=2 |N=2 |O=1
|MolarMass= 343.21
|Appearance= off-white crystalline powder
|Density= 1.381 g/cm3
|MeltingPtC= 143
|Solubility= 4.6 mg/L (20 °C)
|LogP= 2.96
}}
|Section3={{Chembox Hazards
|GHSPictograms = {{GHS09}}
|GHSSignalWord =
|HPhrases = {{H-phrases|H411}}
|PPhrases = {{P-phrases|273|391|501}}
}}
}}
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.{{cite web |url=https://www3.epa.gov/pesticides/chem_search/ppls/007969-00197-20221108.pdf |title=Endura fungicide |publisher=EPA |date=2002-11-08 |access-date=2023-08-10 }} The compound is an biphenyl amide derived inhibitor of succinate dehydrogenase.{{cite web |url=https://www.fao.org/fileadmin/user_upload/IPM_Pesticide/JMPR/Evaluations/2006/Boscalid.pdf |title=Boscalid |first=He |last=Yibing |date=2006 |access-date=2023-08-10 |publisher=FAO }}
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. Many companies made analogues with the aim of expanding the range of species controlled and boscalid was successful in doing so.{{cite book |doi=10.1002/9783527693931.ch31 |chapter=Fungicidal Succinate-Dehydrogenase-Inhibiting Carboxamides |title=Bioactive Carboxylic Compound Classes: Pharmaceuticals and Agrochemicals |year=2016 |last1=Walter |first1=Harald |editor-last1=Lamberth |editor-first1=Clemens |editor-first2=Jürgen |editor-last2= Dinges |publisher=Wiley |pages=405–425 |isbn=9783527339471 }}{{cite web |url=https://www.frac.info/frac-teams/working-groups/sdhi-fungicides/information |title=History of SDHI-fungicides |website=frac.info |access-date=2023-07-26 }}
Synthesis
The first synthesis of boscalid was disclosed in patents filed by BASF in 1995.{{cite patent |country=US |number=5589493 |status=patent |title=Anilide derivatives and their use for combating botrytis |pubdate=1996-12-31 |fdate=1995-06-07 |pridate=1995-06-07 |invent1=Eicken, K |invent2=Goetz, N |invent3=Harreus, A |invent4=Ammermann, E |assign1=BASF SE }}{{cite journal |doi= 10.1002/adsc.201000646 |url=https://www.academia.edu/download/54413923/adsc.20100064620170912-2977-1mb75lu.pdf |title= Toward a Continuous-Flow Synthesis of Boscalid |date= 2010 |last1= Glasnov |first1= Toma N. |last2= Kappe |first2= C. Oliver |journal= Advanced Synthesis & Catalysis |volume= 352 |issue= 17 |pages= 3089–3097 }}{{cite journal |doi=10.1021/acs.oprd.9b00455 |url=https://par.nsf.gov/servlets/purl/10167085 |title=A Sustainable 1-Pot, 3-Step Synthesis of Boscalid Using Part per Million Level Pd Catalysis in Water |date=2020 |last1=Takale |first1=Balaram S. |last2=Thakore |first2=Ruchita R. |last3=Mallarapu |first3=Rushil |last4=Gallou |first4=Fabrice |last5=Lipshutz |first5=Bruce H. |journal=Organic Process Research & Development |volume=24 |pages=101–105 |s2cid=212964123 }}
The aminobiphenyl required for reaction with the acid chloride of 2-chloronicotinic acid is prepared in two steps. The first is a palladium-catalysed Suzuki reaction with 1-chloro-2-nitrobenzene and 4-chloro-phenylboronic acid, followed by hydrogenation of the nitro group. As the final product has been manufactured at the multi-tonne scale, considerable efforts have been made to improve yields.
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.{{cite journal |doi=10.1074/jbc.M311876200 |doi-access=free |title=The Quaternary Structure of the Saccharomyces cerevisiae Succinate Dehydrogenase |year=2004 |last1=Oyedotun |first1=Kayode S. |last2=Lemire |first2=Bernard D. |journal=Journal of Biological Chemistry |volume=279 |issue=10 |pages=9424–9431 |pmid=14672929 }}{{cite journal |doi=10.1016/j.cropro.2010.02.019 |title=Progress in understanding molecular mechanisms and evolution of resistance to succinate dehydrogenase inhibiting (SDHI) fungicides in phytopathogenic fungi |year=2010 |last1=Avenot |first1=Hervé F. |last2=Michailides |first2=Themis J. |journal=Crop Protection |volume=29 |issue=7 |pages=643–651 }}
Usage
Boscalid has fungicidal effects against a wide range of crop pests. These include Alternaria, grey mold (Botrytis cinerea), white mold (Sclerotinia sclerotiorum), and powdery mildew (Uncinula necator). As a result, it has use in crops including fruits, soybeans and vegetables.
The estimated annual use of boscalid in US agriculture is mapped by the US Geological Survey and shows that it is mainly applied to fruit crops, with a maximum use of over {{convert|600000|lb|kg}} in 2016.{{cite web |url=https://water.usgs.gov/nawqa/pnsp/usage/maps/show_map.php?year=2019&map=BOSCALID&hilo=L&disp=Boscalid
|title=Estimated Agricultural Use for boscalid, 2019 |author=US Geological Survey |date=2021-10-12 |access-date=2023-08-10 }} Global sales in 2014 were estimated at $390 million. The compound lacks full control of important cereal diseases, especially septoria leaf blotch Zymoseptoria tritici, which has limited its potential.
Human safety
Boscalid has low acute toxicity: the Codex Alimentarius database maintained by the FAO lists the maximum residue limits for it in various food products.{{cite web |url=https://www.fao.org/fao-who-codexalimentarius/codex-texts/dbs/pestres/pesticide-detail/en/?p_id=221 |title=Boscalid |author=FAO / WHO }}
Environmental effects
The compound is very persistent in field conditions and its environmental fate and consequent ecotoxicology have been reviewed.
Resistance management
Fungal populations have the ability to develop resistance to SDHI inhibitors.{{cite journal |doi=10.1094/pdis-03-20-0487-re |title=Identification and Characterization of Fungicide Resistance in Botrytis Populations from Small Fruit Fields in the Mid-Atlantic United States |year=2021 |last1=Cosseboom |first1=Scott |last2=Hu |first2=Mengjun |journal=Plant Disease |volume=105 |issue=9 |pages=2366–2373 |pmid=33719541 |s2cid=232231834 |doi-access=free }} This potential can be mitigated by careful management. Reports of individual pest species becoming resistant are monitored by manufacturers, regulatory bodies such as the EPA and the Fungicides Resistance Action Committee (FRAC).{{cite web |url=https://www.frac.info/ |title=Fungicides Resistance Action Committee website}} 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.{{cite web |url=https://www.frac.info/fungicide-resistance-management/by-fungicide-common-name |title=Search Fungicides to find FRAC Recommendations |access-date=2020-09-04 }}
Brands
Boscalid is the ISO common name for the active ingredient which is formulated into the branded product sold to end-users. It was also known as nicobifen.{{cite web |url=http://www.bcpcpesticidecompendium.org/boscalid.html |title=Compendium of Pesticide Common Names: Boscalid |publisher=BCPC |access-date=2023-07-27}} Endura and Emerald are the brand names first used by BASF's formulations but the compound has subsequently been sold under a range of product names.
References
{{Reflist}}
External links
- [http://sitem.herts.ac.uk/aeru/ppdb/en/Reports/86.htm PPDB] pesticides properties database entry for boscalid
Category:Disubstituted pyridines