Strobilurin#Synthetic strobilurins

Strobilurins are a group of natural products and their synthetic analogs. A number of strobilurins are used in agriculture as fungicides. They are part of the larger group of QoI (Quinone outside Inhibitors), which act to inhibit the respiratory chain at the level of Complex III.

The first parent natural products, strobilurins A and B, were extracted from the fungus Strobilurus tenacellus.{{cite journal |doi=10.1002/cber.19781110806 |title=Antibiotika aus Basidiomyceten, III. Strobilurin a und B, antifungische Stoffwechselprodukte aus Strobilurus tenacellus |year=1978 |last1=Schramm |first1=Georg |last2=Steglich |first2=Wolfgang |last3=Anke |first3=Timm |last4=Oberwinkler |first4=Franz |journal=Chemische Berichte |volume=111 |issue=8 |pages=2779–2784 }}

Commercial strobilurin fungicidesPeter Jeschke, Matthias Witschel, Wolfgang Krämer, Ulrich Schirmer (eds.): Modern Crop Protection Compounds, 3rd edition, Wiley-VCH, 2019, {{ISBN|978-3-527-34089-7}}. were developed through optimization of photostability and activity.{{cite journal |doi=10.1002/(SICI)1521-3773(19990517)38:10<1328::AID-ANIE1328>3.0.CO;2-1 |title=Strobilurins: Evolution of a New Class of Active Substances |year=1999 |last1=Sauter |first1=Hubert |last2=Steglich |first2=Wolfgang |last3=Anke |first3=Timm |journal=Angewandte Chemie International Edition |volume=38 |issue=10 |pages=1328–1349 |pmid=29711574 }}

Strobilurins represented a major development in fungus-based fungicides. First released in 1996, there are now ten major strobilurin fungicides on the market, which account for 23-25 % of the global fungicide sales.

{{Cite journal

| title = Activity of Two Strobilurin Fungicides Against Three Species of Decay Fungi in Agar Plate Tests

| pages = IRG/WP 17-30704

| author = Juliet D. Tang, Tina Ciaramitaro, Maria Tomaso-Peterson, Susan V. Diehl

| journal = Proc. IRG Annual Meeting

| year = 2017}}

([https://www.fpl.fs.fed.us/documnts/pdf2017/fpl_2017_tang001.pdf pdf link])

Examples of commercialized strobilurin derivatives are azoxystrobin, kresoxim-methyl, picoxystrobin, fluoxastrobin, oryzastrobin, dimoxystrobin, pyraclostrobin and trifloxystrobin.

Strobilurins are mostly contact fungicides with a long half time as they are absorbed into the cuticle and not transported any further. They have a suppressive effect on other fungi, reducing competition for nutrients; they inhibit electron transfer in mitochondria, disrupting metabolism and preventing growth of the target fungi.{{cite book |doi=10.1007/978-3-642-54461-3_8 |chapter=Agrochemicals: 8.2 Strobilurins |title=Natural Products in the Chemical Industry |year=2014 |last1=Schaefer |first1=Bernd |pages=688–704 |isbn=978-3-642-54460-6 }}

Natural strobilurins

=Strobilurin A=

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Strobilurin A (also known as mucidin) is produced by Oudemansiella mucida, Strobilurus tenacellus, Bolinea lutea, and others.{{cite journal |last1 =Lorenzen |first1= K. |last2 =Anke | first2 =T. | year =1998 |title=Basidiomycetes as a Source for New Bioactive Natural Products |url=https://books.google.com/books?id=aI_3BDcYKXgC&pg=PA329 | pages=329–364 |editor-last1=Mori |editor-first1=Kenji |journal=Current Organic Chemistry |volume=2 |issue=4 |doi= 10.2174/1385272802666220128213627 |s2cid= 246934805 |issn=1385-2728 }}{{cite book |doi=10.1007/978-3-662-10378-4_5 |chapter=Non-β-Lactam Antibiotics |title=Industrial Applications |year=2002 |last1=Anke |first1=T. |last2=Erkel |first2=G. |pages=101–104 |isbn=978-3-642-07481-3 }}{{cite journal | last1=Zakharychev | first1=Vladimir V | last2=Kovalenko | first2=Leonid V | title=Natural compounds of the strobilurin series and their synthetic analogues as cell respiration inhibitors | journal=Russian Chemical Reviews | volume=67 | issue=6 | date=1998-06-30 | issn=0036-021X | doi=10.1070/rc1998v067n06abeh000426 | pages=535–544 | bibcode=1998RuCRv..67..535Z | s2cid=95676421}} When first isolated it was incorrectly assigned as the E E E geometric isomer but was later identified by total synthesis as being the E Z E isomer, as shown.{{cite book |doi=10.1007/978-3-642-54461-3_8 |chapter=Agrochemicals: 8.2 Strobilurins |title=Natural Products in the Chemical Industry |year=2014 |last1=Schaefer |first1=Bernd |pages=688–704 |isbn=978-3-642-54460-6 }}{{rp|694}}

==9-Methoxystrobilurin A==

9-Methoxystrobilurin A is produced by Favolaschia spp.

=Strobilurin B=

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Strobilurin B is produced by S. tenacellus.

=Strobilurin C=

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Strobilurin C is produced by X. longipes and X. melanotricha.

=Strobilurin D and G=

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Strobilurin D is produced by Cyphellopsis anomala. Its structure was originally incorrectly assigned and is now considered to be identical to that of strobilurin G, produced by B. lutea. A related material, hydroxystrobilurin D, with an additional hydroxyl group attached to the methyl of the main chain is produced by Mycena sanguinolenta.

=Strobilurin E=

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Strobilurin E is produced by Crepidotus fulvotomentosus and Favolaschia spp.

=Strobilurin F2=

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Strobilurin F2 is produced by B. lutea.

=Strobilurin H=

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Strobilurin H is produced by B. lutea. The natural product with a phenolic hydroxy group in place of the aromatic methoxy group of strobilurin H is called strobilurin F1 and is found in C. anomala and ''Agaricus spp.

=Strobilurin X=

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Strobilurin X is produced by O. mucida.

=Oudemansins=

The oudemansins are closely related to the strobilurins and are also quinone outside inhibitors.

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Oudemansin A with R1 = R2 = H was first described in 1979, after being isolated from mycelial fermentations of the basidiomycete fungus Oudemansiella mucida.{{cite journal |doi=10.7164/antibiotics.32.1112 |pmid=528381 |title=Antibiotics from basidiomycetes. IX. Oudemansin, an antifungal antibiotic from Oudemansiella mucida (Schrader ex Fr.) hoehnel (Agaricales) |journal=The Journal of Antibiotics |volume=32 |issue=11 |pages=1112–1117 |year=1979 |last1=Anke |first1=Timm |last2=Hecht |first2=Hans Jürgen |last3=Chramm |first3=Georgs |last4=Steglich |first4=Wolfgang |doi-access=free }}

Later it was found in cultures of the basidiomycete fungi Mycena polygramma and Xerula melanotricha. The latter fungus also produces oudemansin B, with R1 = MeO and R2 = Cl. Oudemansin X, with R1 = H and R2 = MeO was isolated from Oudemansiella radicata.

Synthetic strobilurins

The discovery of the strobilurin class of fungicides led to the development of a group of commercial fungicides used in agriculture. Examples are shown below.

Image:Azoxystrobin.svg|{{center|Azoxystrobin}}

Image:Trifloxystrobin.svg|{{center|Trifloxystrobin}}

Image:Kresoxim-methyl-2D-skeletal.png|{{center|Kresoxim methyl}}

Image:Pyraclostrobin.png|{{center|Pyraclostrobin}}

See also

References

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