Chromones isoflavones

A similar route to 3-substituted chromones and isoflavone (R = Ph) Scheme 5.10 relies upon a Claisen-Hke condensation between the enolate of a 2-hydroxyphenyl ketone and ethyl formate (methanoate) (Scheme 5.11). 

Dipole moments of flavone (22) and isoflavone (64) have been calculated as a function of the angle by which the phenyl ring is rotated out of the plane of the chromone moiety (B-77MI22200). Correlation of the observed and calculated moments occurs when the ring is turned through less than 30° in the case of flavone, but through approximately 50° for the other flavonoid, and it thus appears that neither molecule is planar. 

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). 

Several groups have described syntheses of chromones which involve the use of enamines. Reaction of salicylaldehyde with 1-morpholinocyclohexene gives the chromanol which is readily oxidized to the chromone (66JOC1232). Other examples include the use of 1-morpholino-l-phenylethylene which gives flavene, whilst N-styrylmorpholine yields isoflavone. The enamine reaction is considered to proceed in the normal manner with subsequent cyclization involving the neighbouring phenolic group (Scheme 163). 

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). 

Vaclavikova et al. [216] have investigated the effect of 13 flavonoid derivatives—aurones, chalcones, flavones, flavonols, chromones, and isoflavones—on 14 C-paclitaxel transport in two human breast cancer cell lines, the doxorubicin-resistant NCI/ADR-RES and sensitive MDA-MB-435. The compounds with known binding affinity toward the NBD of P-gp were selected. The four aurones studied most effectively inhibited P-gp-related transport in the resistant fine in comparison with other groups of flavonoids. The aurones also most effectively increased the intracellular accumulation of paclitaxel and decreased its efflux. The results obtained did not always correlate with the binding of flavonoid derivatives to P-gp, so this indicated that the binding was not the only factor influencing the transport of paclitaxel. The different aspects of inhibition of P-gp by polyphenols was recently reviewed by Kitagawa [212],... 

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>. 

The base-catalyzed rearrangement of aromatic ort/70-acyloxyketones to the corresponding aromatic (3-diketones is known as the Baker-Venkataraman rearrangement. 3-Diketones are important synthetic intermediates, and they are widely used for the synthesis of chromones, flavones, isoflavones, and coumarins. The most commonly used bases are the following KOH, potassium fert-butoxide in DMSO, Na metal in toluene, sodium or potassium hydride, pyridine, and triphenylmethylsodium. 

The rearrangements of phenols which are accompanied by hydroxy group transpositions are called the Wessely-Moser reaction (equations 50 and 51). In essence, these rearrangements are recyclizations of flavonoides 114 via the ring-opened form 115 to give the novel structures 116. Compounds that can participate in these rearrangements are flavones (114, R = H, R = Aryl), flavonoles (114, R = OH, R = Aryl), isoflavones (114, R = Aryl, R = H), chromones (114, R = H, R = Alkyl), chromonoles (114, R = OH, R = Alkyl), xanthones (114, R R = benzo) as well as benzopyrylium salts (e.g. see Reference 95). 

Isoflavones result from a Suzuki coupling reaction with 3-iodochromones (Scheme 11) <05TL3707> and ring expansion of chromones by treatment with Me3SiOTf and a diazoester affords 2,3-benzoxepins via the benzopyrylium salt and cyclopropane derivative <05TL4057>. 

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. ... 

Isoflavones (3-aryl-chromones) can also be prepared in this way boron trifluoride-catalysed Friedel-Crafts acylation of a reactive phenol with an aryl acetic acid is followed by reaction with dimethylfor-mamide and phosphorus pentachloride. ... 

Table 13. Attractant Effect of a Chromone, Two 7-O-Methylflavones, and Two Isoflavones on Zoospores of Aphanomyces cochlioides...

Chromones. 3-Substituted chromones, including isoflavones (3-arylchro-niones), can be prepared in fair to excellent yields by treatment of 2-hydroxy-phcnyl alkyl (arylalkyl) ketones (I) with BF3 etherate (exothermic reaction) in DMF. Metlianesulfonyl chloride in DMF (Vilsmeier reagent) is then added at 52 and (he reaction is warmed on a steam bath (90 minutes). Chromones (2) arc obtained in 65 96% yield. The function of BF , etherate is to deactivate the hydroxylalcd aromatic ring hy complex formation and thus prevent ring lormylalion. 

---