Isoxazole is an electron-rich

azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. T ...

with an

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

atom Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons. Every solid, liquid, gas, ...

next to the

nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...

. It is also the class of compounds containing this ring. Isoxazolyl is the univalent radical derived from isoxazole.

Occurrence

Isoxazole rings are found in some natural products, such as

ibotenic acid Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compound and psychoactive drug which occurs naturally in ''Amanita muscaria'' and related species of mushrooms typically found i ...

and

muscimol Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of '' Amanita muscaria'' and related species of mushroom. Muscimol is a potent and selective orthosteric agonist for the GABAA receptors and displa ...

Synthesis

Isoxazole can be synthesised via a variety of methods. Examples include via a 1,3-dipolar cycloaddition of

nitrile oxide In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix '' cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...

s with alkynes; or the reaction of

hydroxylamine Hydroxylamine is an inorganic compound with the formula . The material is a white crystalline, hygroscopic compound.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Professional Publishing Ltd. pp. 431–43 ...

with 1,3-diketones or derivatives of propiolic acid.

Photochemistry

The photolysis of isoxazole was first reported in 1966. 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.

Pharmaceuticals and herbicides

Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor

valdecoxib Valdecoxib is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, and painful menstruation and menstrual symptoms. It is a selective cyclooxygenase-2 inhibitor. It was patented in 1995. V ...

( Bextra) and a neurotransmitter agonist

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

. A derivative,

furoxan Furoxan or 1,2,5-oxadiazole 2-oxide is a heterocycle of the isoxazole family and an amine oxide derivative of furazan. It is a nitric oxide donor. As such, furoxan and its derivatives are actively researched as potential new drugs and insensitive ...

, is a nitric oxide donor. An isoxazolyl group is found in many beta-lactamase-resistant antibiotics, such as

cloxacillin Cloxacillin is an antibiotic useful for the treatment of a number of bacterial infections. This includes impetigo, cellulitis, pneumonia, septic arthritis, and otitis externa. It is not effective for methicillin-resistant ''Staphylococcus aureus ...

dicloxacillin Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria.Product Information: DICLOXACILLIN SODIUM-dicloxacillin sodium capsule. T ...

and

flucloxacillin Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to t ...

. Leflunomide is an isoxazole-derivative drug. Examples of AAS containing the isoxazole ring include

danazol Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken by mouth. The use of danazol is limited by masculin ...

and

androisoxazole Androisoxazole (brand names Androxan, Neo-Ponden, Neo-Pondus), also known as 17α-methyl-5α-androstano,2-csoxazol-17β-ol, is an orally active anabolic-androgenic steroid (AAS) and a 17α-alkylated derivative of dihydrotestosterone (DHT) that ...

. A number of pesticides are isoxazoles. left, Isoxaben is an example of an isoxazole used as a herbicide.

References

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External links