Flavan derivatives

Most flavan derivatives occur in plants as glycosides. The sugars are attached to the hydroxyls of the A ring and of the heterocycle, attachment to the hydroxyl of the C atom 3 occurring particularly frequently. 

Chalcones are not flavan derivatives since they lack the characteristic central heterocycle. They are converted spontaneously into true flavan derivatives, the flavanones, the reacjtion occurring particularly readily in acidic medium. They play a central role in the biosynthesis of the flavan derivatives. Chalcone glycosides oceur in relatively high quantities in the flowers of several of the Compositae and Leguminosae, which, as a result. 

Chalcone Ftavanone Flavone Ftavonol Catechin Flavan-3.4- Anthocyanid in 

Flavones possess one double bond more than the flavanones in their central heterocycle. The white meal on shoots and leaves of Pri-mulaceae, such as the bird s eye primrose Primula farinosa, consists, in part, of the parent compound, flavone itself. However, derivatives of flavone such as apigenin and luteolin (Fig. 106) are much more widely occurring. 

If a hydroxyl group is introduced into the 3-position of the central ring of flavones, flavonols are obtained. Biosynthetically, however, they are not produced in this way (Fig. 110). Flavonol glycosides lend a whitish to pale yellow tinge to flowers. Their occurrence is in no way limited to the flower, they are found in all other parts of the plant. Their ubiquitous occurrence suggests a central function for the flavonols, although up to now the hypotheses based on this supposition are poorly founded. Thus, it is assumed that some flavonols are inhibitors, others activators, of the lAA oxidase (page 198). 

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Takashima, J. and Ohsaki, A., Acutifolins A-F, a new flavan-derived constituent and five new flavans from Brosimum acutifolium, J. Nat. Prod., 64, 1493, 2001. 

Clark-Lewis, J.H., Flavan derivatives. XXI. Nuclear magnetic resonance spectra, configuration and conformation of flavan derivatives, Aust. J. Chem., 21, 2059, 1968. 

Clark-Lewis, J.W. and Mortimer, P.I., Flavan derivatives. III. Melacacidin and isomelacacidin from Acacia species, J. Chem. Soc., 4106, 1960. 

Flavan derivatives. Part II. The relative configurations of catechin and epicatechin 1,2-rearrangement in the reduction of the diastereoisomers to the same enantiomorph of a propan-l-ol. J. chem. Soc. [London] 1960, 2433. 

Components The phytochemistry of the individual classes varies enormously [for components of the clubmosses and horse tails, see the appropriate entries]. The true ferns (Filicatae) contain saccharose as the main carbohydrate. Large amounts of C2o-poly-enoic acids, see also arachidonic acid, and fatty acids with 21 - 30 C atoms are found among the lipids. Ferns produce a great variety of secondary products such as procyanidins, condensed tannins, flavan derivatives, benzoic and cinnamic acid derivatives, acylphloroglucinols, cyanogenic glycosides, pter-osins, di- and triterpenes as well as phytoecdysone (see ecdysteroids). Alkaloids have not yet been detected. 

Phenylpropane amino acids Cinnamic acid, coumarins, lignin, lignans, flavan derivatives, stilbenes, phenolcarboxylic acids, phenols, components of volatile oils. 

Flavane derivatives Flavonoids (D 22.3.3) Feeding stimulant for Scolytus mediterraneus (beetle), Bombyx mori larvae (silkworm) and many other insects... 

Baig M, Clark-Lewis J W, Thompson M J 1969 Flavan derivatives. XXVII. Synthesis of a new racemate of leucocyanidin tetramethyl ether (2,3-c/s-3,4-fra 5 isomer) NMR spectra of the four racemates of leucocyanidin tetramethyl ether (5,7,3, 4 -tetramethoxyflavan-3,4-diol). Aust J Chem 22 2645-2650... 

Clark-Lewis J W, Dainis I 1964 Flavan derivatives. XL Teracacidin, melacacidin, and 7,8,4 -trihydroxy flavanol from Acacia sparsifolia and extractives from Acacia ovites. Aust J Chem 17 1170-1173... 

Clark-Lewis J W, Dainis I 1967 Flavan derivatives. XIX. Teracacidin and isoteracacidin from ca-cia obtusifolia and Acacia maidenii heartwoods Phenolic hydroxylation patterns of heartwood flavonoids characteristic of sections and subsections of the genus Acacia. Aust J Chem 20 2191-2198... 

Clark-Lewis J W, Katekar G F, Mortimer PI 1961 Flavan derivatives. IV. Teracacidin, a new leu-coanthocyanidin from Acacia intertexta. J Chem Soc 499-503... 

Vilian C, Damas J, Lecompte J, Foo L Y 1985 Pharmacological properties of a novel flavan derivative isolated from the New Zealand conifer Phyllocladus alpinus. Cardiovascular activities of phylloflavan in rats. In Proc 7th Hungarian Bioflavonoid Symp Szeged Hungary... 

Clark-Lewis J W, Dainis I 1968 Flavan derivatives. 20. A new glycoside and other extractives from Acacia ixiophylla Rhamnitrin (Rhamnetin 3a-L-rhamnoside). Aust J Chem 21 415-420... 

Clark-Lewis J W, Korytnyk W 1958 Flavan derivatives. Part 1. The absolute configuration of (+)-dihydroquercetin. J Chem Soc 2367-2372... 

Flavan derivatives are characterized by the flavan skeleton. It consists of an aromatic ring A, an aromatic ring B, and a central, oxygen-contain-... 

The acetate-malonate pathway. This is used to synthesize the aromatic ring A of the flavan derivatives. Otherwise this route is more important for microorganisms. 

Fig. 105. Survey of several flavan derivatives. Above, the basic skeleton. Below, the central heterocycle of several groups of flavan derivatives.

First let us take another glance at the structural formulae of the individual anthocyanidins. We notice that the pattern of substitution in ring B is the same as that which we have already encountered with the cinnamic acids, the coumarins and the phenol carboxylic acids. In retrospect we may notice that this observation holds true for the whole group of the flavan derivatives, though the parallels are usually easier to see than here... 

Fig. 109. Hypothesis concerning the formation of the 15-C skeleton of the flavan derivatives.

Modifications of the Heterocycle (Fig, 770). In the next step the open chain structure is closed to form ring A. We obtain the kind of substance which we recognize, namely, a chalcone. Isotope experiments, especially those of Grisebach, have removed all doubt that such chalcones are the parent substances of all flavan derivatives. The chalcones are converted to flavones and all of the subsequent reaction sequences up to the anthocyanidins consist only of appropriate modifications of the central ring system. We should realize that the elucidation of the biosynthesis of the anthocyanins implies at the same time an understanding of the biosynthesis of all flavan derivatives. This is because the individual flavan derivatives are either precursors of the anthocyanins or they can be derived from such precursors. 

The problem remains unsolved. Some biochemical findings support one mechanism, others support the other. Perhaps both possibilities are operative, depending on the plant. However, data on the occurrence of different flavan derivatives in one plant and genetic findings are not compatible with the second possibility. 

Let us summarize biosynthetically the flavan derivatives are hybrid substances. Their A ring is derived from acetate, their B ring and the C atoms 2, 3 and 4 of the heterocycle from phenylpropanes. The 15 C skeleton is probably synthesised from malonyl CoA and cinnamic acid CoA compounds, the reaction sequence being analogous to the acetate-malonate pathway. 

We are now familiar with the carotenoids and the flavan derivatives and they represent the most important flower pigments. Carotenoids are responsible for yellow to red colors and flavan derivatives for whitish, yellow, red, and blue colors. Anthocyanins are the red and blue flavan pigments. 

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