Flavones and Isoflavones

KAO Y c, ZHOU c, SHERMAN M, LAUGHTON 0 A, CHEN s (1998) Molecular basis of the inhibition of human aromatase (oestrogen synthetase) by flavone and isoflavone phytoestrogens a site-directed mutagenesis study. Environ Health Perspect. 106 85-92. 

Many higher plants synthesize flavanes, flavanones, flavones, and isoflavones with a wide range of structural complexity. They make a significant contribution to the food intake of both herbivores and humans, and they have aroused particular interest on account of their degradation by mammals that are mediated by intestinal bacteria. Most of them exist naturally as glycosides and these are readily hydrolyzed to the aglycones. 

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

The basic structures of flavanones, flavones, and isoflavones together with coumestrol, an intermediate in the phenylpropane metabolism, are given in Fig. 2. The 3,5,7,3 -tetrahydroxy-4 -methoxyflavanone is a nod gene inducer in Rhizo-bium leguminosarum bv. viciae the 3, 4, 5,7-tetrahydroxyflavone, in Rhizobium ineliloti and 4,7-dihydroxyisoflavone, in Bradyrhizobium japonicum. Coumestrol, an intermediate in phenylpropane metabolism, is only a weak inducer (7). 

Root flavonoids that may act as signals for the initiation and development of endomycorrhizal and ectomycorrhizal symbio.ses have been identified (see Chap. 7). Metabolites of the phenylpropanoid pathways apparently act as signaling molecules in endo- and ectomycorrhizal interactions (14). The role of flavonoids is still controversial, but a variety of flavanones, flavones, and isoflavones... 

Koch-Haaf reaction, 17, 3 Kornblum oxidation, 39, 3 Kostaneki synthesis of chromanes, flavones, and isoflavones, 8, 3... 

Aral, Y. et al.. Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration, J. Nutr., 130, 2243, 2000. 

Kamperdick, C. et al., Flavones and isoflavones from Millettia ichthyochtona. Phytochemistry, 48, 577, 1998. 

Of the classes of compounds discussed in this chapter the chromones (1 R Ph), including flavones and isoflavones (1 R = 2-Ph and R = 3-Ph), and coumarins (2) are the most numerous. Many of these compounds are found in plants and there is a wide variety of structures amongst them. There appears not to be a single well-defined biological role for... 

Chromones are readily oxidized by permanganate or dichromate with opening of the pyran ring and the formation of a salicylic acid (402). Flavones and isoflavones are also degradatively oxidized for example oxidation of munetone (403) with alkaline hydrogen peroxide yields 2-methoxybenzoic acid and 4-hydroxy-2-isopropylbenzofuran-5-carboxylic (isotubaic) acid. 

Under normal reaction conditions (heating the reactants with or without a solvent in an alkaline medium) the pyranone ring of chromones, flavones and isoflavones is opened at... 

Pyran-4-ones and their monobenzo derivatives undergo ring opening when treated with aqueous alkali. This reaction has been widely used in the investigation of structure of chromones, flavones and isoflavones but xanthones are little affected. The nucleophile attacks the 1,2-bond in a rate-determining step whose rate constant varies with the electron density in the ground state at C-2. A kinetic study of the reaction with several chromones supports the mechanism shown in Scheme 25 (79ACH(101)73). 

The parent nucleus of the flavonoids is flavone ((58), 2-phenylchromone or 2-phenylbenzopyran-4-one). Flavone and isoflavone ((59), 3-phenylchromone, the parent nucleus of the isoflavonoids) are the simplest oxygen-containing naturally occurring compounds that possess the 2-phenylnaphthalene -type structure. The chalcones, represented by the nucleus (60), may be regarded as open-chain flavonoids and are usually hydroxylated. The interconversion of chalcone and flavonone catalyzed by chalcone isomerase is well known [326, 327, 331], Chalcones can be precursors of both the flavonoids and the isoflavonoids [326-332]. 

Few of these species are strictly aromatic, but reactivity with electrophiles resembles that of aromatic compounds. Much of the discussion that follows will be devoted to the pyrones and thiopyrones (the fused benz-derivatives, coumarins, chromones, flavones, and isoflavones, will be covered in Part 3). 

Chromones, flavones, and isoflavones of general types 396 and 398 have been reported to undergo reduction with nickel borohydride in dry methanol at ambient temperatures to give the corresponding 277-l-benzopyran-4-ols in good yields. In all cases studied, the products obtained were found to be the air-stereoisomers, for example, 397 and 399 (Scheme 64) <2002JCM201>. 

Flavones and Isoflavones, Their Dihydro Derivatives and Related Compounds... 

Losses of small molecules and/or radicals from [M+H]" are observed in the positive-ion mode losses of HjO, CO, and HjC=C=0, and combinations thereof. The loss of a methyl radical CHj is characteristic for O-methylated isoflavones, flavones, and flavonols [13]. Loss of C4H8 indicates the presence of prenyl substituents (at 3-, 6-, and/or 8-position) [t4]. Kuhn et al. [t5] demonstrated the differentiation between isomeric flavones and isoflavones by means of positive-ion MS-MS in an ion-trap instmment. tsoflavones show an abundant fragment ion due to the loss of 2 CO molecules from the C-ring, while flavones only show a single CO loss. 

Flavones and isoflavones (3-aryl-chromones) are quantitatively converted into 2,3-epoxides by exposure to dimethyl dioxirane flavone oxides are quantitatively converted by acid into 3-hydroxy-flavones, which are naturally occurring. ... 

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