Flavonoid methyl ethers

Masayuki, S., D. DiFeo JR., N. Nakatani, B. Timmermann, and T. J. Mabry Flavonoid Methyl Ethers on the External Leaf Surface of Larrea tridentata and L. divaricata. Phytochemistry 15, 727 (1976). 

Phlomis consists of about 100 species, a dozen of which occur in Mediterranean Europe (Mabberley, 1997, p. 549). The study of interest here involves a study of the flavonoids of R lychnitys L., a small plant native to Mediterranean Spain (Tomas et ah, 1986). Those workers identified the common flavones apigenin, luteolin, and luteolin 3 -methyl ether (chrysoeriol) 7-0-glucosides and their respective /7-coumaroyl derivatives. A brief review of the literature revealed that Mediterranean species of Phlomis are characterized by the presence of the flavone methyl ether, whereas continental species appear to lack 0-methylated flavones. Species from India have been reported to lack flavones but accumulate flavonols. The suggestion was made that accumulation of flavonols represents an ancestral feature of the genus. 

Additional information on chemical variation within this species came from studies of exudate and internal (vacuolar) pigments based on broader collections of the fern (Star et al., 1975a, b). Exudate flavonoids, identified from specimens representing the range of the species, were identified as ceroptene [221], the C-methylflavonol pityrogrammin [222], and two derivatives of kaempferol, the 4 -methyl ether [223] and the 7,4 -dimethyl ether [224] (see Fig. 2.69 for stmctures 221-224). 

Catechol-O-methyltransferase (COMT EC 2.1.1.6) is located in many tissues and catalyzes the methylation of polyphenols. The methylation is a well-established pathway in the metabolism of flavonoids such as those that undergo 3, 4 -dihydrox-ylation of ring B excreted as 3 -0-methyl ether metabohtes in rat bile. " Recently, the apparent methylation of both cyanidin-3-glucoside and cyanidin-3-sambubioside (cyanidin is an anthocyanin with a 3, 4 -dihydroxylation of ring B) to peonidin-3-glucoside and peonidin-3-sambubioside was reported in humans. In rats, this transformation occurred mainly in the liver and was catalyzed by COMT."°... 

Havonoids are made up of a number of classes of very similar groups in which two phenyl rings are connected by a three-carbon unit [10], The open structure members are yellow in color and termed as chalcones, and simple cyclization to a furanoid structure deepens the color to the orange aurones. The most usual flavonoids are, however, the pale-yellow flavones and flavonols, or 3-hydroxyflavones, which will be treated here, and the red-blue anthocyanins, which will be treated in the next section. Figure 13.4 shows examples of these main classes and their structural relationships. The natural compounds of all classes often occur as glycosides and as methyl ethers. 

Flavonoid sulphates such as quercetin 3,7-di-O-methyl 3-sulphate and kaempferol 7-0-methyl 3-sulphate, which inhihited the growth of Mycobacterium tuberculosis and Klebsiella pneumoniae, were isolated from the -hutanol fraction of 80% methanol extract of Argyreia speciosa (Burm. f) Boj. (Convolvulaceae), while flavonoids with mti-Helicobacter pylori activity, such as quercetin 3-methyl ether (isorhamnetin) (Fig. 3), were isolated from Cistus laurifolius L. (Cistaceae). ... 

Van Rensburg, H. et al., Enantioselective synthesis of flavonoids. Part 3. Trans- and cw-flavan-3-ol methyl ether acetates, J. Chem. Soc., Perkin Trans. 1, 3415, 1997. 

Species of the genus Vellozia have been extensively studied for their flavonoid complement in relation to chemosystematics. In addition to a series of C-methylflavonols and two C-prenylated flavonols, derivatives of vellokaempferol and velloquercetin are accumulated in whole plants, leaves, and leaf exudates. The basic structure of these compounds is characterized by 7,6-isopropenylfurano substitution, based upon kaempferol, quercetin, and their 0-methyl ethers. In addition, 8-C-methyl derivatives of these compounds were also identified from leaves of V. stipitata " So far, species of this genus are the only reported sources of these compounds, which in parts have been proved to be accumulated externally. ° Structures are exemplified by Figure 12.10. 

By comparison, a series of mostly monoacylated flavonols is known to date and recent reports increased the number slightly. Four new products came from Pseudognaphalium robustum and Tanacetum microphyllum (both Asteraceae), and from Adina cordifolia (Rubia-ceae). A diacetylated compound (3,5-diacetyltambulin) was recently isolated from the bark of Zanthoxylum integrifoliolum (Rutaceae). Since most of the flavonols are monoacylated, the accumulation of quercetin tetraacetate in Adina cordifolia is a remarkable result. Altogether, the newly reported compounds occur scattered in the plant kingdom their occurrence is so far of little chemosystematic value. Aerial parts of Tanacetum microphyllum (Asteraceae) yielded a derivative, which is structurally not an ester. It is, indeed, a carbo-methoxy derivative of 6-hydroxyluteolin-4 -methyl ether (compound 34 in Table 12.5). No other flavonoid of this type is known so far. 

Figure 6.8 Regioselective deacylation of the polyacetilated flavonoid quercetin (28a) by action of different lipases (CalB, lipase from Candida antarctica Mml, lipase from Mucor miehei f-BME, ferf-butyl methyl ether)...

In typical flavonoids one of the meta-hydroxyl groups of the A-ring contributes the oxygen to the six atom-heterocycle. The six member oxygen heterocycle of typical flavonoids may be a pyran (1.30), pyrylium (1.31), or pyrone ring (1.32). The B-ring is typically mono-hydroxylated, ortho-dihydroxylated, or v/c-trihydroxylated. The B-ring may also have methyl-ethers as substituents. 

Recent reviews122 124 have reported the natural occurrence of more than 150 sulfated flavonoids in some 300 species belonging to several dicot and monocot families. These are mostly mono- to tetrasulfate esters of common hydroxyflavones and hydroxyflavonols and their methyl ethers and less commonly of their... 

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