Of flavone

Chrysin (17) was the first flavone to be isolated in a pure form, and its stmcture was elucidated by identification of its alkaline degradation products (72—74). The stmcture was confirmed by synthesis (75,76). The same procedures were used to estabflsh the stmcture of other flavones and in so doing the foundation of flavone chemistry was laid (77). 

Although the literature refers to the formation of chromones/coumarins as the Kostanecki reaction (and often the Kostanecki-Robinson reaction) and the synthesis of flavones as the Allan-Robinson reaction, others have chosen to merge the two reactions and refer to both transformations as the Kostanecki-Robinson reaction. This section will follow the latter school of thought, and use the Kostanecki-Robinson (K-R) nomenclature. 

The synthesis of flavones has also seen modifications over the years. One of the primary modifications has been substituting the carboxylate salt for other bases. Kohn and Low showed that catalytic amounts of triethylamine allowed for the reaction to be run at 160 Looker and coworkers expanded on the Kohn and Low modification by using amines as the solvent, and thus reduced the reaction temperatures. They typically found that the reaction could be run at the refluxing temperatures of the amine. They showcased this modification by converting oi-methoxyphloroacetophenone (35) to the methyl ether of galangin (36) using a variety of amines in 60-75% yield with benzoic anhydride. 

Horie and coworkers synthesized a series of flavones that showed promising inhibitory activity against archidonate 5-lipooxygenase. This enzyme is responsible for the initiation of bioactive leukotrienes that are chemical mediators of anaphylaxis and inflammation. Under standard K-R conditions o-hydroxyarylketone 66 and anhydride 67 in presence of the corresponding anhydride 68 delivered flavones 69 in yields of 42-65%. Subsequent hydrogenation of 69 afforded the flavone inhibitors 70. 

The two examples given here will be the determination of flavones in grapefruit juice and the measurement of histamine in rat brain. 

A solvent-free synthesis of flavones was recently reported by microwave-assisted reaction of phloroglucinol 231 and differently substituted /1-ketoesters 232 [148]. The reaction was simply carried out by mixing the phenol and the ester in an open test tube followed by irradiation for 2-3 min. The internal temperature reached 240 °C and yields were in the range from 68 to 96%. Scheme 85 describes the application of this procedure to the synthesis of the natural product chrysin 233. 

Table 5.1 Comparison of flavones of Conocephalum conicum specimens from North America and Germany...

RUSZNYAK s and szent-gyOrgi a (1936) Vitamin nature of flavones . Nature, 139, 798. 

Ibrahim A-R S, YJ Abul-Hajj (1990a) Microbiological transformation of flavone and isoflavone. Xenobiotica 20 363-373. 

Table 1 Antimutagenic Effects of Flavones on Mutagenicity Induced by IQ IN Salmonella typhimurium TA98...

Stermitz, F. R. Adamovics, J. A. Geigert, J. Synthesis and photoreactions of sorbo-phenones a photochemical synthesis of flavones. Tetrahedron 1975, 31, 1593-1595. 

A solvent-free synthesis of flavones has been achieved that simply involves the MW irradiation of o-hydroxydibenzoylmethanes adsorbed on montmorillonite K 10 clay for 1-1.5 min. A rapid and exclusive formation of cyclized flavones occurs in good yields (Scheme 6.41) [140], The intramolecular Michael addition of o-hydroxy-... 

Scheme 6.41 Formation of flavones by cyclization of o-hydroxydibenzoylmethanes on l< 10 clay.

In Greece, a case-control study was conducted to investigate the incidence of liver cancer by estimating the consumption of six types of flavonoids with a semiquantitative questionnaire on the frequency of foods. The intake of flavones was inversely associated with hepatocellular carcinoma, irrespective of its etiology (viral or nonviral). With respect to cholangiocarcinoma, an inverse association with the consumption of flavan-3-ols, anthocyanidins, and total flavonoids studied was found. However, this last result should be viewed with caution because of the small sample size, due to the fact that this is a rare type of cancer (Lagiou and others 2008). 

An efficient synthesis of flavones, which occurs without formation of the corresponding aurone, involves the carbonylative cyclisation of oacetoxyiodophenols and arylalkynes (Scheme 48) . A large scale, one-pot synthesis of isoflavones has been described <00SC469>. 

Flavonoids are secondary metabolites generally occurring in various plants as glycosides. The chemical structure of flavonoids shows high variety. The basic structure of flavons and flavonols is the 2-phenylbenzo-gamma-pyrone. Flavonoids generally contain two phenol rings linked with a linear three-carbon chain (chalcones) or with three carbon... 

Fig. 2.38. Basic chemical structure of flavones, flavonols and flavonoids (chalcones and aurones).

A simple TLC method has been developed for the separation and identification of flavons and flavon glycosides in the extract of Phillyrea latifolia L. The leaves (100 g) were defatted in 11 of chloroform for 24 h and then extracted with 2 X 11 of ethanol-water (80 20, v/v). The collected extracts were concentrated and extracted again with n-hexane to remove chlorophylls and other apolar constituents. Analytes were extracted with ethyl acetate. Both normal phase and RP-TLC have been used for the separation of flavonoids. The results are compiled in Table 2.36. It was concluded from the data that TLC can be successfully applied for the quality control of plant extracts containing various flavone derivatives [124],... 

TLC DATA OF THE ISOLATED COMPOUNDS AND OF FLAVONE, FLAVONE GLYCOSIDE AND BIFLAVONE REFERENCE STANDARDS... 

A. Pieroni, D. Heimler and Y. Huand, A TLC method for the separation and identification of flavons and flavon glycosides from biflavons in vegetable extract. J. Plan. Chromatogr.—Mod. TLC. 11 (1998) 230-232. 

S.M. Boue, C.H. Carter-Wientjes, B.Y. Shih and T.E. Cleveland, Identification of flavone aglycones and glucosides in soybean pods by liquid chromatography-tandem mass spectrometry. J. ChromatogrA 991 (2003) 61-68. 

IVpical syntheses of flavones under liquid liquid phase-transfer catalysis... 

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