Isoxazoles, isomer of oxazoles, are a series of five-membered heterocycle compounds containing adjacent N atom and O atom. The main difference in the aspect of structure of isoxazoles compared with oxazoles is the relative position of N and O. Isoxazoles possess typical characteristic of arene due to their aromatic ring structure. What’s more, heterocyclic structure might decomposes under alkaline conditions, which can be attributed to weak N-O bond. The special property makes them possible to act as a construction unit of a variety of organic compounds. There are two main approaches to synthetize isoxazoles: 1. 1,3-dipolar addition between alkyne or alkene and nitric oxide. However, the low yield and regioselectivity and harsh reaction conditions hamper its practical application. 2. Annulation of hydroxylamine with compounds containing three carbon atoms such as 1,3-diketones and α,β-unsaturated carbonyl compound. The disadvantage of this method is expensive catalyst used in this transformation although with moderate yield and wide substrate applicability.
Isoxazoles have low water solubility because active groups (-OH, -NH2) are not contained in their structure despite with two heteroatoms. Different isoxazoles derivatives can be obtained via tuning the steric and electronic properties of substitutes attached to aromatic C atoms. Most isoxazoles exhibit low melting point and high boiling point, thus Isoxazoles are a class of colorless odorous liquid at room temperature whose characters are similar to pyridine.
Organic synthesis. Isoxazoles are an important class of intermediate in organic synthesis. Ring-opening reaction of isoxazoles can provide a number of difunctional compounds which play significant role in constructing organic structure. In addition, the synthesis of Brefeldin, a Macrolide fungal metabolites with excellent biological activity, constitutes the formation of isoxazoles intermediate. Similarly, isoxazoles structure is also involved in the preparation of FR-900482 analogue.
(J. Org. Chem., 2002, 67, 764-771)
(Org. Lett., 2001, 3(16), 2575-2578)
Medicine. Isoxazoles have attracted extensive attention in prevention and treatment of various diseases due to theirs unique pharmacological activity. Isoxazoles exhibit excellent biological activity towards the target of diseases. And it is worthy noting that isoxazoles are important skeleton structure of lots of diabetic active molecule. Besides, isoxazoles can be uitilized in curing osteoporosis, angiocardiopathy and Alzheimer’s Disease.
(J. Med.Chem., 2011, 54(1), 233-247)
(J. Med.Chem., 2008, 51(20), 6318-6333)
Agricultural application. Numerous isoxazoles derivatives have been used as herbicide, bactericide and insecticide and so on. The study for isoxazoles derivatives with herbicidal activity displays a huge role in the field of developing new herbicide. Some isoxazoles derivatives also possess outstanding insecticide activity. For example, isoxathion is useful for preventing aphids and multi pests including rice fulgorid and rice-stem borer. Apart from inhibiting growth of pests, it can also promote plant growth through the absorption of root of plant.