Chemistry:Flavones
Flavones (from Latin flavus "yellow") are a class of flavonoids based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) (as shown in the first image of this article).[1][2]
Flavones are common in foods, mainly from spices, and some yellow or orange fruits and vegetables.[1] Common flavones include apigenin (4',5,7-trihydroxyflavone), luteolin (3',4',5,7-tetrahydroxyflavone), tangeritin (4',5,6,7,8-pentamethoxyflavone), chrysin (5,7-dihydroxyflavone), and 6-hydroxyflavone.[1]
Intake and elimination
The estimated daily intake of flavones is about 2 mg per day.[1] Following ingestion and metabolism, flavones, other polyphenols, and their metabolites are absorbed poorly in body organs and are rapidly excreted in the urine, indicating mechanisms influencing their presumed absence of metabolic roles in the body.[1][3]
Drug interactions
Flavones have effects on CYP (P450) activity,[4][5] which are enzymes that metabolize most drugs in the body.
Biosynthesis
The biosynthesis of flavones proceeds from the phenylpropanoid pathway, which uses L-phenylalanine as a starting point.[6] Phenylalanine ammonia lyase facilitates the deamination of L-phenylalanine to (E)-cinnamate,[6] which is then oxidized by cinnamate 4-hydroxylase to yield p-Coumaric acid.[7] Coenzyme A is attached to the carboxylate facilitated by 4-Coumarate-CoA ligase, forming (Coumaroyl-CoA).[6] A chalcone synthase then facilitates a series of condensation reactions in the presence of 3 malonyl CoA ending with a ring-forming Claisen condensation yielding a chalcone (naringenin chalcone is shown), [8] which is subsequently isomerized by chalcone isomerase resulting in a flavanone (naringenin is shown).[9] It is at this point that the flavanone can undergo further modifications (such as glycosylation or methylation at the various points of the backbone. The subsequent modified flavanones are then transformed into flavones by flavone synthase, which generates a double bond between the C-2 and C-3 positions (the synthesis of apigenin is shown).[10]
Organic chemistry
In organic chemistry several methods exist for the synthesis of flavones:
- Allan–Robinson reaction
- Auwers synthesis
- Baker–Venkataraman rearrangement
- Algar–Flynn–Oyamada reaction
Another method is the dehydrative cyclization of certain 1,3-diaryl diketones.[11]
Wessely–Moser rearrangement
The Wessely–Moser rearrangement (1930)[12] has been an important tool in structure elucidation of flavonoids. It involves the conversion of 5,7,8-trimethoxyflavone into 5,6,7-trihydroxyflavone on hydrolysis of the methoxy groups to phenol groups. It also has synthetic potential for example:[13]
This rearrangement reaction takes place in several steps: A ring opening to the diketone, B bond rotation with formation of a favorable acetylacetone-like phenyl-ketone interaction and C hydrolysis of two methoxy groups and ring closure.
Common flavones
| Name | Structure | R3 | R5 | R6 | R7 | R8 | R2' | R3' | R4' | R5' | R6' |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Flavone backbone | 
|
– | – | – | – | – | – | – | – | – | – |
| Primuletin | – | –OH | – | – | – | – | – | – | – | – | |
| Chrysin | – | –OH | – | –OH | – | – | – | – | – | – | |
| Tectochrysin | – | –OH | – | –OCH3 | – | – | – | – | – | – | |
| Primetin | – | –OH | – | – | –OH | – | – | – | – | – | |
| Apigenin | – | –OH | – | –OH | – | – | – | –OH | – | – | |
| Acacetin | – | –OH | – | –OH | – | – | – | –OCH3 | – | – | |
| Genkwanin | – | –OH | – | –OCH3 | – | – | – | –OH | – | – | |
| Echioidinin | – | –OH | – | –OCH3 | – | –OH | – | – | – | – | |
| Baicalein | – | –OH | –OH | –OH | – | – | – | – | – | – | |
| Oroxylin A | – | –OH | –OCH3 | –OH | – | – | – | – | – | – | |
| Negletein | – | –OH | –OH | –OCH3 | – | – | – | – | – | – | |
| Norwogonin | – | –OH | – | –OH | –OH | – | – | – | – | – | |
| Wogonin | – | –OH | – | –OH | –OCH3 | – | – | – | – | – | |
| Liquiritigenin[15] | – | – | – | –OH | – | – | – | –OH | – | – | |
| Naringenin[15] | – | –OH | – | –OH | – | – | – | –OH | – | – | |
| Geraldone | – | – | – | –OH | – | – | –OCH3 | –OH | – | – | |
| Tithonine | – | – | – | –OCH3 | – | – | –OH | –OCH3 | – | – | |
| Luteolin | – | –OH | – | –OH | – | – | –OH | –OH | – | – | |
| 6-Hydroxyluteolin | – | –OH | –OH | –OH | – | – | –OH | –OH | – | – | |
| Chrysoeriol | – | –OH | – | –OH | – | – | –OCH3 | –OH | – | – | |
| Diosmetin | – | –OH | – | –OH | – | – | –OH | –OCH3 | – | – | |
| Pilloin | – | –OH | – | –OCH3 | – | – | –OH | –OCH3 | – | – | |
| Velutin | – | –OH | – | –OCH3 | – | – | –OCH3 | –OH | – | – | |
| Norartocarpetin | – | –OH | – | –OH | – | –OH | – | –OH | – | – | |
| Artocarpetin | – | –OH | – | –OCH3 | – | –OH | – | –OH | – | – | |
| Scutellarein | – | –OH | –OH | –OH | – | – | – | –OH | – | – | |
| Hispidulin | – | –OH | –OCH3 | –OH | – | – | – | –OH | – | – | |
| Sorbifolin | – | –OH | –OH | –OCH3 | – | – | – | –OH | – | – | |
| Pectolinarigenin | – | –OH | –OCH3 | –OH | – | – | – | –OCH3 | – | – | |
| Cirsimaritin | – | –OH | –OCH3 | –OCH3 | – | – | – | –OH | – | – | |
| Mikanin | – | –OH | –OCH3 | –OCH3 | – | – | – | –OCH3 | – | – | |
| Isoscutellarein | – | –OH | – | –OH | –OH | – | – | –OH | – | – | |
| Zapotinin | – | –OH | –OCH3 | – | – | –OCH3 | – | – | – | –OCH3 | |
| Zapotin | – | –OCH3 | –OCH3 | – | – | –OCH3 | – | – | – | –OCH3 | |
| Cerrosillin | – | –OCH3 | –OCH3 | – | – | – | –OCH3 | – | –OCH3 | – | |
| Alnetin | – | –OH | –OCH3 | –OCH3 | –OCH3 | – | – | – | – | – | |
| Tricetin | – | –OH | – | –OH | – | – | –OH | –OH | –OH | – | |
| Tricin | – | –OH | – | –OH | – | – | –OCH3 | –OH | –OCH3 | – | |
| Corymbosin | – | –OH | – | –OCH3 | – | – | –OCH3 | –OCH3 | –OCH3 | – | |
| Nepetin | – | –OH | –OCH3 | –OH | – | – | –OH | –OH | – | – | |
| Pedalitin | – | –OH | –OH | –OCH3 | – | – | –OH | –OH | – | – | |
| Nodifloretin | – | –OH | –OH | –OH | – | – | –OCH3 | –OH | – | – | |
| Jaceosidin | – | –OH | –OCH3 | –OH | – | – | –OCH3 | –OH | – | – | |
| Cirsiliol | – | –OH | –OCH3 | –OCH3 | – | – | –OH | –OH | – | – | |
| Eupatilin | – | –OH | –OCH3 | –OH | – | – | –OCH3 | –OCH3 | – | – | |
| Cirsilineol | – | –OH | –OCH3 | –OCH3 | – | – | –OCH3 | –OH | – | – | |
| Eupatorin | – | –OH | –OCH3 | –OCH3 | – | – | – | –OCH3 | –OH | – | |
| Sinensetin | – | –OCH3 | –OCH3 | –OCH3 | – | – | – | –OCH3 | –OCH3 | – | |
| Hypolaetin | – | –OH | – | –OH | –OH | – | –OH | –OH | – | – | |
| Onopordin | – | –OH | – | –OH | –OCH3 | – | –OH | –OH | – | – | |
| Wightin | – | –OH | – | –OCH3 | –OCH3 | –OCH3 | –OH | – | – | – | |
| Nevadensin | – | –OH | –OCH3 | –OH | –OCH3 | – | – | –OCH3 | – | – | |
| Xanthomicrol | – | –OH | –OCH3 | –OCH3 | –OCH3 | – | – | –OH | – | – | |
| Tangeretin | – | –OCH3 | –OCH3 | –OCH3 | –OCH3 | – | – | –OCH3 | – | – | |
| Serpyllin | – | –OH | – | –OCH3 | –OCH3 | –OCH3 | –OCH3 | –OCH3 | – | – | |
| Sudachitin | – | –OH | –OCH3 | –OH | –OCH3 | – | –OCH3 | –OH | – | – | |
| Acerosin | – | –OH | –OCH3 | –OH | –OCH3 | – | –OH | –OCH3 | – | – | |
| Hymenoxin | – | –OH | –OCH3 | –OH | –OCH3 | – | –OCH3 | –OCH3 | – | – | |
| Gardenin D | – | –OH | –OCH3 | –OCH3 | –OCH3 | – | –OH | –OCH3 | – | – | |
| Nobiletin | – | –OCH3 | –OCH3 | –OCH3 | –OCH3 | – | –OCH3 | –OCH3 | – | – | |
| Scaposin | – | –OH | –OCH3 | –OH | –OCH3 | – | –OCH3 | –OCH3 | –OH | ||
| Name | Structure | R3 | R5 | R6 | R7 | R8 | R2' | R3' | R4' | R5' | R6' |
Research
In one preliminary 2021 study, flavone intake was associated with lower odds of subjective cognitive decline after adjustment for age, total energy intake, major nondietary factors, and specific dietary factors.[16]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Flavonoids". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. November 2015. http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids.
- ↑ "Flavone". ChemSpider, Royal Society of Chemistry. 2015. http://www.chemspider.com/Chemical-Structure.10230.html.
- ↑ David Stauth (5 March 2007). "Studies force new view on biology of flavonoids". EurekAlert!; Adapted from a news release issued by Oregon State University. http://www.eurekalert.org/pub_releases/2007-03/osu-sfn030507.php.
- ↑ "The potential of flavonoids to influence drug metabolism and pharmacokinetics by local gastrointestinal mechanisms". Curr Drug Metab 7 (7): 729–744. Oct 2006. doi:10.2174/138920006778520570. PMID 17073577.
- ↑ "Mechanism of CYP2C9 inhibition by flavones and flavonols". Drug Metab. Dispos. 37 (3): 629–34. March 2009. doi:10.1124/dmd.108.023416. PMID 19074529.[1]
- ↑ 6.0 6.1 6.2 "Structure and function of enzymes involved in the biosynthesis of phenylpropanoids". Plant Physiol. Biochem 46 (3): 356–370. 2008. doi:10.1016/j.plaphy.2007.12.009. PMID 18272377.
- ↑ "Isolation of a cDNA and a genomic clone encoding cinnamate 4-hydroxylase from Arabidopsis and its expression manner in plants". Plant Physiology 113 (3): 755–763. 1997. doi:10.1104/pp.113.3.755. PMID 9085571.
- ↑ "Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis". Nat. Struct. Biol. 6 (8): 775–784. 1999. doi:10.1038/11553. PMID 10426957.
- ↑ "Structure and mechanism of the evolutionarily unique plany enzyme chalcone isomerase". Nat. Struct. Biol. 7 (9): 786–791. 2000. doi:10.1038/79025. PMID 10966651.
- ↑ "Flavones and flavone synthases". Phytochemistry 66 (20): 2399–2407. 2005. doi:10.1016/j.phytochem.2005.07.013. PMID 16137727.
- ↑ "A facile synthesis of flavones using recyclable ionic liquid under microwave irradiation". Arkivoc xvi (16): 43–8. 2006. doi:10.3998/ark.5550190.0007.g05.
- ↑ "Synthese und Konstitution des Skutellareins". Monatshefte für Chemie 56 (1): 97–105. December 1930. doi:10.1007/BF02716040.
- ↑ "A convenient extension of the Wessely-Moser rearrangement for the synthesis of substituted alkylaminoflavones as neuroprotective agents in vitro". Bioorg. Med. Chem. Lett. 10 (8): 835–8. April 2000. doi:10.1016/S0960-894X(00)00110-4. PMID 10782697. https://hal.archives-ouvertes.fr/hal-02385135/file/Accepted%20Bioorg.%20Med.%20Chem.%202000.pdf.
- ↑ Harborne, Jeffrey B.; Marby, Helga; Marby, T. J. (1975). The Flavonoids - Springer. doi:10.1007/978-1-4899-2909-9. ISBN 978-0-12-324602-8.
- ↑ 15.0 15.1 Dewick, Paul M. (2009). "The Shikimate Pathway: Aromatic Amino Acids and Phenylpropanoids". Medicinal Natural Products. A Biosynthetic Approach. Chichester, UK: John Wiley & Sons. pp. 137-186. doi:10.1002/9780470742761.ch4. ISBN 978-0-470-74276-1.
- ↑ Yeh, Tian-Shin; Yuan, Changzheng; Ascherio, Alberto; Rosner, Bernard A.; Willett, Walter C.; Blacker, Deborah (2021-09-07). "Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women" (in en). Neurology 97 (10): e1041–e1056. doi:10.1212/WNL.0000000000012454. ISSN 0028-3878. PMID 34321362.
External links
- Flavones at the US National Library of Medicine Medical Subject Headings (MeSH)
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