Flavones, formation

Flavone formation is believed to proceed through a similar mechanism as the synthesis of chromones, albeit aromatic acid anhydrides and their corresponding salts are used. The first step is benzoylation of 12 to give the ester 14. Enolization and o-alkylation then affords the enolbenzoate 15. Enolbenzoate 15 then undergoes an acyl transfer to yield... 

The analogous palladium catalyzed reaction of internal acetylenes, 2-iodophenol and carbon monoxide leads to the selective formation of coumarins. The heterocyclic analogues of o-iodophenol are also effective. The o-iodopyridone shown in 4.16. for example gave rise to the formation of azacoumarin in 70% yield.18 In these processes the insertion of the acetylene derivative occurs in advance of the insertion of CO. Interestingly, the change of the acetylene to an alkene reverses the insertion order and leads to flavone formation.19... 

However, the flavanone naringenin (10) [but not dihydro-kaempferol (13)] is the substrate for flavone formation in snapdragons. Antirrhinum majus (Scrophulariaceae) (flavone synthase II) (Fig. 11.10). In this plant, flavones arise from dehydrogenation of flavanones and not from dehydration of dihydroflavonols (Britsch et al., 1981). A similar enzyme system converts dihydroflavonols to flavonols (Britsch et al., 1981). In other work, the enzyme responsible for oxidation of flavanones to flavones in snapdragon Antirrhinum majus) was isolated from a microsomal fraction and shown to require NADPH and molecular oxygen (Britsch et al., 1981 Dewick, 1989 Forkmann and Stotz, 1981). The system appears to be a cytochrome P-450-dependent monooxygenase. This system also is known from Glycine max... 

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106[127]. The ben-zofuran 107 is formed from 2-allyIphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdChf S], Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

Kojic acid — see also Pyran-4-one, 5-hydroxy-2-hydroxymethyl-, 3, 611 acylation, 3, 697 application, 3, 880 occurrence, 3, 692 reactions, 3, 714, 715 with amines, 3, 700 with phenylhydrazine, 3, 700 synthesis, 3, 810 Kokusagine occurrence, 4, 989 Kokusaginine occurrence, 4, 989 synthesis, 4, 990 Koopmans theorem, 2, 135 Kostanecki-Robinson reaction chromone and coumarin formation in, 3, 819-821 mechanism, 3, 820 flavones, 3, 819... 

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. 

R] (a) Hauser, C. R. Swamer, F. W. Adams, J. T. Org. React. 1954, 8, 59. [R] (b) Ellis, G. P., Chromenes, Chromanones, and Chromones from The Chemistry of Hetereocylic Compounds, Weissberger, A. and Taylor, E. C., eds John Wiley Sons, 1977, vol. 31, New York, p.495. Note The author in the former reference refers to the formation of chromones, coumarins, and flavones as the Kostanecki acylation while the latter author calls the formation of chromones and coumarins the Kostanecki-Robinson reaction. 

The mechanisms of the cyclisation of 2 -hydroxychalcone derivatives which can lead to flavanones, flavones and aurones have been reviewed <95MI1> and the formation of 3-hydroxy- chromanones and -flavanones from l-(2-hydroxyphenyl)-2-propen-l-ones via the epoxide has been optimised <96JOC5375>. 

Each plant tissue tends to have an obviously distinctive profile of flavonoids. The flavonoid content can reach about 0.5% in pollen, 10% in propolis, and about 6 mg/kg in honey. Havonoid aglycones appear to be present only in propolis and honey, while pollen contains flavanols in herosidic forms. The flavonoids in honey and propolis have been identified as flavanones and flavanones/flavanols (Campos et ah, 1990). The antimi-crobially active flavanone pinocembrine was foimd to be a major flavonoid in honey (Bogdanov, 1989). Amiot et ah (1989) studied two blossom and two honeydew Swiss honey samples and foimd that pinocembrine was the main flavonoid. Pinocembrine concentration varied between 2 and 3 mg/kg (Bogdanov, 1989). Berahia et ah (1993) analyzed sunflower honey samples and detected six flavone/flavols, four flavanone/ flavols, and pinocembrin, of which pinocembrin is the main flavonoid. The flavonoids in sunflower honey and propolis were characterized and assessed for their effects on hepatic drug-metabolizing enzymes and benzo [fl]pyrene-DNA adduct formation (Sabatier et ah, 1992 Siess et ah, 1996). 

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.

An improvement in the Baker-Venkataraman route to flavonols (2-aryl-3-hydroxychromones) which avoids a final oxidation step of the flavone involves formation of... 

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>. 

There are many branches to the flavonoid biosynthetic pathways, with the best characterized being those leading to the colored anthocyanins and proanthocyanidins (PAs) and the generally colorless flavones, flavonols, and isoflavonoids. Genes or cDNAs have now been identified for all the core steps leading to anthocyanin, flavone, and flavonol formation, as well as many steps of the isoflavonoid branch, allowing extensive analysis of the encoded enzymes (Table 3.1). In addition, several DNA sequences are available for the modification enzymes that produce the variety of structures known within each class of compound. 

The key enzymes involved in the formation of the hydroxycinnamic acids (HCAs) from phenylalanine and malonyl-CoA are now discussed in detail, while later sections address the branches of the flavonoid pathway leading to anthocyanins, aurones, flavones, flavonols, PAs, and isotlavonoids. This is followed by brief reviews of the regulation of flavonoid biosynthesis and the use of flavonoid genes in plant biotechnology. To assist the reader. Figure 3.1 presents the carbon numbering for the various flavonoid types discussed. 

A desaturation reaction forming a double bond between C-2 and C-3 of the C-ring is involved in the formation of both flavones and flavonols, and the respective substrates involved, (25)-flavanones and (2R,3R)-DHFs, differ only in the presence or absence of the 3-hydroxyl (Figure 3.2). 

Approaches to inhibit anthocyanin production that target CHS can cause plant sterility, as flavonols play a role in fertility in some species. It is possible to inhibit anthocyanin production by targeting an enzyme such as DFR, which still allows the formation of flavonols and flavones. Sense or antisense DFR transgenes have been used to reduce or prevent anthocyanin production in several species (Table 3.4), with results similar to those for CHS... 

The genus Tephrosia (Fabaceae) was selected to demonstrate the biosynthetic capacity of flavone substitution. In particular, there is a strong tendency towards formation of furano-residues, linked through C-bonds on position 8 of the flavone nucleus (e.g., apollinine, hookerianin Figure 12.5). The basic flavone structure is mostly 5- and 7-O-methylated. These compounds have been exclusively reported to occur in roots, leaf and stem as well as... 

Data on this type of flavonols are summarized in Table 12.4. In contrast to the corresponding flavones, the number and complexity of derivatives is smaller. This concerns particularly the formation of furano-, pyrano- and other cyclic flavonols. There is a remarkable number of 0-prenylated flavonols known to date, contrasting to only very few flavones exhibiting this substitution pattern (see Table 12.3). Similar trends have been earlier documented in the review of Barron and Ibrahim. The occurrence of a series of glycosides based on C-prenylated structures is considerable. This substitution trend concerns also some of the dihydroflavonols, thus indicating specific enzyme activities probably dependent on the presence of a 3-OH group. 

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