In Vitro Flavon-3-ol Oxidation Mediated by a B Ring Hydroxylation Pattern

Abstract

Flavonols are potent naturally occurring antioxidants. Chemical oxidation reactions in combination with modern spectroscopic techniques have been employed to identify oxidized flavonoid products. Although many oxidized derivatives have been generated from commercially available starting materials, few studies have developed a sequence of flavonoid substrates with a particular hydroxylation pattern to probe the mechanism of flavonoid oxidation. Here, we use AIBN (2,2'-azobisisobutyronitrile) in combination with a series of hydroxylated flavonols to probe the mechanism of flavonoid dimer formation and the role of singly or doubly oxidized species in generating and promoting oxidized flavonoid products. 3-Methoxyquercetin (3-hydroxyl group blocked) and luteolin (lack of 3-hydroxyl) were reacted with AIBN alone or with a second flavonol to serve as a C-3 hydroxyl donor to examine the mechanism of dimer formation. 3-Hydroxyflavones with increasing hydroxyl substitutions in the B ring were also reacted with AIBN in the presence or absence of an external nucleophile to examine the role of various hydroxyls in the formation of a carbocation intermediate via a doubly oxidized species. The presence of a free C-3 hydroxyl, coupled with a B ring ortho hydroxy unit, appears essential for dimer formation. An increase in the number of hydroxyls in the B ring facilitates products generated from a doubly oxidized species.

Identification of the Products of Oxidation of Quercetin by Air Oxygenat Ambient Temperature

“…The same products were isolated in the result of quercetin oxidation by hydrogen peroxide under the same pH conditions. The formation of the aforementioned products is in complete agreement with literature data on the oxidation of quercetin under different conditions [14][15][16][17][18][19][20][21][22][23][24][25][26][27]. To date the oxidative decarbonylation of 1 was considered the likely process which could take place preferably in non-aqueous solvents in the presence of strong bases and often at above-ambient temperatures (in pyridine during 14 h [14], in dimethylformamide with additives of potassium tert-butoxide at 37 °C during 3 h [16], etc.).…”

“…Similar processes of oxidative destruction of 3-hydroxyflavones (including quercetin) by air oxygen with the formation of the same products were observed under catalysis by the enzymes quercetinase [16] and tyrosinase [17], in the presence of radical initiators like azodiisobutyronitrile [18][19][20] or the CuSO 4 /H 2 O 2 system [21], and in the complexes of flavonols with Cu 2+ ions [22,23]. The same degradation products were detected as a result of γ-irradiation of quercetin solutions [24,25] and even heating of its solutions at the presence of oxygen [26,27].…”

“…This allows us to classify 1 as more unstable than the well-known ascorbic acid, which is inert to contact with air under the same conditions. Of course, there is a high probability that the products of this reaction should be the same as established previously [14][15][16][17][18][19][20][21][22][23][24][25][26][27], but this should be confirmed independently. In addition there is the problem is the origin of gaseous products formed in this reaction (CO or CO 2 ), because the oxidative state of carbon in these oxides determines the possible mechanism of the process.…”

Dimerisation Process of Silybin-Type Flavonolignans: Insights from Theory

“…[4,[20][21][22] The oxidation-induced dimerisation of polyphenols is a wellknown mechanism in plants. [23,24] It can be the initiation step of oligomerisation (e.g.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Chromone (chromen-4-one or 1,4-benzopyrone) derivatives, exemplified by compounds like 87-89 ( Figure 6) are widespread in Nature, particularly in flowers as pigments, and have interesting biological activities such as antiviral, [84], antioxidant [85,86], anti-inflammatory [87,88], and anticancer properties [89]. Some of them have been also reported as kinase inhibitors [90,91].…”