Naturally occurring isoxazoles

A review of isoxazole compounds (covering the period 1963—1977) discusses their synthesis, reactivity, and physiological and physicochemical properties naturally occurring and biologically active isoxazoles are included.27 Some Saudi Arabian plants have been screened for alkaloids.28 Aristolochic acids I (28 R = H) and D (28 R = OH), which are cytotoxic to mammalian systems, are also cytotoxic to non-tumorous plant cells.29... 

At the time of the earlier review many biologically active isoxazole and reduced isoxazole derivatives had been reported, including the naturally occurring antituberculosis antibiotic cycloserine (119), the monoamine oxidase inhibitor isocarboxazid (120), and isoxazolosteroids showing anabolic... 

Intramolecular nucleophilic substitution of electrogenerated phenoxonium ions has been investigated . In connection with naturally occurring bromo compounds, methyl 3,5-dibromo-4-hydroxyphenyl pyruvate oxime (98) was subjected to anodic oxidation (-1-1.3 V Vi. SCE 2.1 Fmol ) in MeOH to afford spiro-isoxazole 99 in almost quantitative yield . Methyl 3-bromo-4-hydroxyphenyl pyruvate oxime (100) was also electrolyzed under similar conditions to give three compounds 101, 102 and 103 in 34, 14 and 17% yields, respectively. The latter two products are formed by C—O and C—C radical couplings, respectively, as shown in Scheme 19 °. 

The biological activity of substituted isoxazoles has made them a focus of medicinal chemistry and the significant pharmaceutical activity of several naturally occurring examples is well-documented <05CRV2723>. Moreover, the facile cleavage of the N-O bond of the isoxazole nucleus under simple reaction conditions is the reason for the numerous applications of this system as synthetic intermediates for the construction of molecular assemblies including different heterocycles and natural products <05CRV4237>. 

Isoxazoles (Problem 36) have taken on increased significance as synthetic targets, because they are found in the structures of some recently discovered naturally occurring molecules that show promise as antibiotics (see Real Life 20-2). Isoxazoles may be prepared by reaction of aUcynes with compounds containing the unusual nitrile oxide functional group ... 

There are several naturally occurring isoxazoles with interesting biological activity. Eor example. Muscimol and 4-hydroxy isoxazole, are seed-germination inhibitors... 

Decarboxylation of isoxazole-3-carboxylic acids is related to the nucleophilic cleavage of the isoxazole ring as far as the nature of the reaction products is concerned. It occurs at temperatures above 200°C and is accompanied by the cleavage of the nitrogen-oxygen bond of the heterocyclic ring to yield a j8-ketonitrile. It was first reported by Claisen with 5-methyl- and 5-phenyl-isoxazole-3-carboxylic acids (153- 154).Under the reaction conditions, j8-ketonitriles condense... 

The reduction of isoxazoles is often rather peculiar and its course depends on the nature both of the isoxazole and of the reducing agent. Together with a normal reduction of groupings in the side chain, cleavage of the nitrogen-oxygen bond of the heterocyclic nucleus often occurs. 

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