:Isoxazole

Isoxazole rings are found in some natural products, such as ibotenic acid and muscimol.

Isoxazole can be synthesised via a variety of methods.{{cite journal | vauthors =Dasa S, Chanda K| title = An overview of metal-free synthetic routes to isoxazoles: the privileged scaffold | journal = RSC Adv | issue = 11 | pages = 32680-32705 | date = 2021 | doi = 10.1039/D1RA04624A | doi-access = free | pmc = 9042182 }}{{cite journal |last1=Morita |first1=Taiki |last2=Yugandar |first2=Somaraju |last3=Fuse |first3=Shinichiro |last4=Nakamura |first4=Hiroyuki |title=Recent progresses in the synthesis of functionalized isoxazoles |journal=Tetrahedron Letters |date=March 2018 |volume=59 |issue=13 |pages=1159–1171 |doi=10.1016/j.tetlet.2018.02.020}}

Examples include via a 1,3-dipolar cycloaddition of nitrile oxides with alkynes; or the reaction of hydroxylamine with 1,3-diketones or derivatives of propiolic acid.{{cite journal | vauthors =Hossain M, Khan M, Kim S, Le H| title = Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides | journal = Beilstein J. Org. Chem. | issue = 18 | pages = 446–458 | date = 2022 | doi = 10.3762/bjoc.18.47 |pmid=35529890 | doi-access = free | pmc = 9039522 }}

The photolysis of isoxazole was first reported in 1966.{{cite journal | author =Edwin F. Ullman| title = Photochemical Transposition of Ring Atoms in Five-Membered Heterocycles. The Photorearrangement of 3,5-Diphenylisoxazole | journal = J. Am. Chem. Soc. |volume = 88 |issue = 8 | pages = 1844–1845 | date = 1966| doi = 10.1021/ja00960a066 }} Due to the weak N-O bond, the isoxazole ring tends to collapse under UV irradiation, rearranging to oxazole through azirine intermediate. Meanwhile, the azirine intermediate can react with nucleophiles, especially carboxylic acids. Given the photoreactions, isoxazole group is developed as a native photo-cross-linker for photoaffinity labeling and chemoproteomic studies.{{cite journal | author1 = Cheng, K. |author2=Qi, J. |author3=Ren, X. |author4=Zhang, J. |author5=Li, H. |author6=Xiao, H. |author7=Wang, R. |author8=Liu, Z. |author9=Meng, L. |author10=Ma, N. |author11=Sun, H.| title = Developing Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics. | journal = Angew. Chem. Int. Ed. |volume=61 |issue= 47 | pages = e202209947 | date = 2022| doi = 10.1002/anie.202209947 }}{{cite journal | author1 = Lougee, M. |author2=Pagar, V. |author3=Kim, H. |author4=Pancoe, S. |author5=Chia, W. |author6=Mach, R. |author7=Garcia, B. |author8=Petersson, E. | title = Harnessing the Intrinsic Photochemistry of Isoxazoles for the Development of Chemoproteomic Crosslinking Methods. | journal = Chem. Comm. |volume= 58 |issue= 65 | pages = 9116-9119 | date = 2022| doi = 10.1039/D2CC02263J |pmc= 9922157 }}

Isoxazoles also form the basis for a number of drugs,{{cite journal|title=The recent progress of isoxazole in medicinal chemistry|author1=Zhu, Jie |author2=Mo, Jun |author3=Lin, Hong-zhi |author4=Chen, Yao |author5=Sun, Hao-peng|journal=Bioorganic & Medicinal Chemistry|year=2018|volume=26|issue=12|pages=3065–3075|doi=10.1016/j.bmc.2018.05.013}} including the COX-2 inhibitor valdecoxib (Bextra) and a neurotransmitter agonist AMPA. A derivative, furoxan, is a nitric oxide donor. An isoxazolyl group is found in many beta-lactamase-resistant antibiotics, such as cloxacillin, dicloxacillin and flucloxacillin. Leflunomide is an isoxazole-derivative drug. Examples of AAS containing the isoxazole ring include danazol and androisoxazole. A number of pesticides are isoxazoles.{{cite journal|journal=Journal of Heterocyclic Chemistry|title=Oxazole and Isoxazole Chemistry in Crop Protection|author=Clemens Lamberth|year=2018|volume=55|issue=9|pages=2035–2045|doi=10.1002/jhet.3252}} Gaboxadol is a conformationally constrained isoxazole derivative of muscimol.

image:Isoxaben.svg is an example of an isoxazole used as a herbicide.]]

• Oxazole, an analog with the nitrogen atom in position 3
• Pyrrole, an analog without the oxygen atom
• Furan, an analog without the nitrogen atom
• Simple aromatic rings

{{reflist}}

• [https://www.organic-chemistry.org/synthesis/heterocycles/isoxazoles.shtm Synthesis of isoxazoles (overview of recent methods)]

{{Chemical classes of psychoactive drugs}}

Category:Simple aromatic rings