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. Th ...

with an

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...

next to the

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

. It is also the class of compounds containing this ring. Isoxazolyl is the univalent

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

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 naturally occurring alpha-amino acid found in certain ''Amanita'' mushrooms, that primarily acts as a potent glutamate receptor agonist ...

and

muscimol Muscimol, also known as agarin or pantherine, as well as 5-(aminomethyl)-1,2-oxazol-3-ol, is the principal psychoactive constituent of ''Amanita muscaria'' and '' Amanita pantherina''. Muscimol is an isoxazole alkaloid and a potent and selectiv ...

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 name of the compound is composed of a base, which includes the carbon of the , suffixed with "nitrile", so for example is called " propionitrile" (or pr ...

s with

alkyne \ce \ce Acetylene \ce \ce \ce Propyne \ce \ce \ce \ce 1-Butyne In organic chemistry, an alkyne is an unsaturated hydrocarbon containing at least one carbon—carbon triple bond. The simplest acyclic alkynes with only one triple bond and n ...

s; or the reaction of

hydroxylamine Hydroxylamine (also known as hydroxyammonia) is an inorganic compound with the chemical formula . The compound exists as hygroscopic colorless crystals.Greenwood and Earnshaw. ''Chemistry of the Elements.'' 2nd Edition. Reed Educational and Prof ...

with 1,3-diketones or derivatives of

propiolic acid Propiolic acid is the organic compound with the formula HC2CO2H. It is the simplest acetylenic carboxylic acid. It is a colourless liquid that crystallises to give silky crystals. Near its boiling point, it decomposes. It is soluble in water a ...

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 A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

, 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 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 ...

) and a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

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 Glutamic acid (symbol Glu or E; kn ...

. A derivative,

furoxan Furoxan (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, such as ipramidil, are being actively studied as potential new ...

, is a

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

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

cloxacillin Cloxacillin is an antibiotic useful for the treatment of several 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. ...

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 ...

. 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 oral administration, by mouth. The use of danazol is ...

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 Pesticides are substances that are used to pest control, control pest (organism), pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for a ...

are isoxazoles.

Gaboxadol Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the alkaloid muscimol (a constituent of ''Amanita muscaria'') that was first synthesized in 1977 by the Danish chem ...

is a

conformationally constrained In chemistry, rotamers are chemical species that differ from one another primarily due to rotations about one or more single bonds. Various arrangements of atoms in a molecule that differ by rotation about single bonds can also be referred to as ...

isoxazole derivative of

. left, Isoxaben is an example of an isoxazole used as a herbicide.

References

External links