Methoxyflavones

Seshradi and coworkers showed that potassium carbonate was an effective base in the K-R reaction for the conversion of resacetophenone (37) to 7-hydroxyflavone 39a and 7-hydroxy-4 -methoxyflavone 39b in 57% and 46% yield, respectively. In addition, the reaction proceeded at a significantly lower temperature than the traditional K-R reaction by conducting the reaction in refluxing acetone. 

In the area of medicinal chemistry, Haemers and coworkers synthesized a series of 4 -hydroxy-3-methoxyflavones that exhibited antiviral activity against poliomyelitis and rhinoviruses. A representative number of compounds is shown below. First, O-hydroxyacetophenones 61 were converted to the corresponding flavones 64 using standard conditions in yields of 74-92%. Cleavage of the benzyloxy groups of 64 was then achieved under acidic conditions to deliver the requisite flavones 65. 

Lemiere and coworkers synthesized the antipicomavirus agent 3-0-Methylquercetin (76). A key transformation was the conversion of acetophenone 61a to 3-methoxyflavone 79. In the event, 61a and 3,4-dibenzyloxybenzoic anhydride (77) were allowed to react at 160 C in the presence of sodium carboxylate 78 to deliver the penultimate intermediate in 78% yield. Debenzylation of 79 in the presence of Pearlman s catalyst delivered the natural product in 99% yield. 

Wolfbeis, O. S. Schipfer, R. Knierzinger, A. pH-dependent fluorescence spectroscopy. Part 12. Flavone, 7-hydroxyflavone, and 7-methoxyflavone. J. Chem. Soc., Perkin Trans. 2 1981, 1443-1448. 

Huen MS, Leung JW, Ng W, et al. Dihydroxy-6-methoxyflavone, a benzodiazepine site ligand isolated from Scutellaria baicalensis Georgi, with selective antagonistic properties. Biochem Pharmacol 2003 66 125-127. 

VI. Isolation of Diosmetin from Crude Apigenin and Its Identification as 5,7,3 -Trihydroxy-4 -methoxyflavone. 63... 

Trihydroxy-4 -methoxyflavone (Diosmetin, Luteolin 4 -methyl ether)... 

The synthesis of 5,7,4 -trihydroxy-3 -methoxyflavone was performed in an analogous way, substituting 0-benzylvanillic anhydride and sodium 0-benzylvanillate in place of the substances of the isovanillic acid series. 

NMR spectroscopy has been used to study flavonoids only in a few cases. Natural abundance NMR spectra have been recorded for 11 methoxyflavones, and NMR data for some 3-arylidenechromanones and flavanones have recently been discussed in terms ofmesomeric and steric substituent interactions. NMR spectroscopy has also been used to study the effect of sugar on anthocyanin degradation and water mobility in a roselle anthocyanin model system. ... 

Baneiji, A. and Luthria, D.L., Assignment of methoxy resonances and observation of restricted rotation of B-ring of 2 -methoxyflavones by 2D-NOESY in conjunction with ASIS, Spectrosc. Lett., 24, 1047, 1991. 

Ma, Y.L., Van den Heuvel, H., and Claeys, M., Characterization of 3-methoxyflavones using fast-atom bombardment and collision-induced dissociation tandem mass spectrometry, Rapid Gommun. Mass Spectrom., 13, 1932, 1999. 

Dihydroxyflavone geraldone (7,4 -dihydroxy-3 -methoxyflavone) 4 -hydroxy-7-methoxyflavone... 

Flavonoids, especially flavones and flavonols, also directly bind to several CYP isoforms (lAl, 1A2, IBl, 3A4) involved in xenobiotics metabolism and inhibit enzyme activity. Structure-activity relationships show rather high isoform selectivities depending on the flavonoid substitution pattern and contrasted inhibition mechanisms. For instance, inhibition by flavonoids of 7-methoxyresorufin O-demethylation in microsomes enriched in CYP lAl and 1A2 reveals that galangin (3,5,7-trihydroxyflavone) is a mixed inhibitor of CYP 1A2 (.ST = 8 nM) and a five times less potent inhibitor of CYP 1A1. By contrast, 7-hydroxy flavone is a competitive inhibitor of CYP lAl (Aii = 15 nM) and a six times less potent inhibitor of CYP 1A2. In addition, fairly selective inhibition of CYP IBl (specifically detected in cancer cells) by some flavonoids has been reported. For example, 5,7-dihydroxy-4 -methoxyflavone inhibits IBl, 1 Al, and 1A2 with IC50 values of 7, 80, and 80 nM, respectively. ... 

Gonzalez, A.G. et al., Methoxyflavones from Ageratum conyzoides. Phytochemistry, 30, 1269, 1991. 

Horie, T. et al., Studies of the selective O-alkylation and dealkylation of flavonoids. XIV. A convenient method for synthesizing 5,6,7,8-trihydroxy-3-methoxyflavones from 6-hydroxy-3,5, 7-trimethoxyflavones, Bull. Chem. Soc. Jpn, 66, 877, 1993. 

Guha, P.K. and Bhattacharyya, A., 5,8-Dihydroxy-7-methoxyflavone from the immature leaves of Didymocarpus pedicellata. Phytochemistry, 31, 1833, 1992. 

Sahu, N.P., Achari, B., and Banerjee, S., 7,3 -Dihydroxy-4 -methoxyflavone from seeds of Acacia farnesiana. Phytochemistry, 49, 1425, 1998. 

Tominaga, H. and Horie, T., Studies of the selective 0-alkylation of flavonoids. XV. A convenient synthesis of 3,5,6-trihydroxy-7-methoxyflavone and revised structures of two natural flavones. Bull. Chem. Soc. Jpn., 66, 2668, 1993. 

Jakobsen, T.H. et al., 3-Methoxyflavones and a novel coumarin from Psiadia dentata, Biochem. Syst. Ecol., 29, 963, 2001. 

Simonsen, H.T. et al., Methylenedioxy- and methoxyflavones from Melicope coodeana syn. Euodia simplex. Phytochemistry, 60, 817, 2002. 

Tahara, S., Hashidoko, Y., and Mizutani, J., New 3-methoxyflavones in the roots of yellow Lupin (Lupinus luteus cv. Topaz), Agric. Biol. Chem., 51, 1039, 1987. 

Rutinoside 6-(4"-Acetylrhamnosyl)(l 6)glucoside 5,7,2 -Trihydroxy-6-methoxyflavone Dicliptera riparia whole plant Acanthaceae 85... 

Pentahydroxy-8-methoxyflavone 7-Glucoside Vellozia nanuzae leaves Velloziaceae 146... 

C-Prenyl-5,7,4 -trihydroxy-3 -methoxyflavone (8-C-prenylchrysoeriol) 7-Glucosyl(l — 3)-a-L-arabinopyranoside Erythrina indica seeds Leguminosae 164... 

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