RÖMPP Encyclopedia Natural Products, 1st Edition, 2000

▶ Table: Substitution pattern of Anthocyanidins.

The variety of the up to 300 reported A. arises through multiple degrees of glycosidation with various hexoses and pentoses as well as from additional acylation with aliphatic and aromatic acids. Further structural differences result from simple conjugation, e. g., glycosidation at C-3 of the pyran ring with formation of monosides and further glycosidation, e.g., at C-5 of the A ring with formation of 3,5-diglycosides (glucosides, galactosides, rhamnosides, arabinosides, and xylosides). Complex aromatic polyacyl conjugates, with long side chains can form folded structures in dependence on the nature and position of the acyl group (hydroxycinnamic acid). A well-known example is “heavenly blue anthocyanin” (HBA) from Ipomoea tricolor (Convolvulaceae). HBA bears a branched group (1,2-glycosidic) at C-3 of peonidins with 5 glucose and 3 caffeic acid units as well as a glucose group at C-5. The caffeic acid groups have ester bonds at C-6 of the glucose-units and a glycosidic bond with one of the phenolic hydroxy groups.

The folded structure of HBA results in a so-called “sandwich stacking” 2 in which the caffeic acids groups are arranged in parallel to peonidin on account of hydrophobic interactions. This is the reason for the phenomenon of the intramolecular copigmentation3, reflected in a marked deepening of the color (bathochromic shift of light absorption). Furthermore, this stacking protects the anthocyanidin from tautomerization and hydration at the average pH values between 4 and 6 in the plant vacuoles. At pH values above 3 the colorless quinoid base forms and can lead to pyran ring opening through addition of water at C-2. The pH-de-pendent color behavior of the A. is a conspicuous indication for tautomerism of the anthocyanidin structure. In acidic aqueous solution, isolated A. exhibit a red to reddish violet color which turns to a blue to bluish-green color upon addition of weak alkali. Stabilization of the anthocyanidin primary structure and protection from water addition in A. that are not protected by intramolecular stacking is achieved either by self-association or by intermolecular stacking (intermolecular copigmentation) with other phenylpropane derivatives, such as, e.g., flavones or hydroxycinnamic acid conjugates.
Use: A. play a major role in food coloring (E 163). The problem of their instability could be solved by use of the considerably more stable polyacylated A.
Biosynthesis: The biosynthesis of anthocyanidins proceeds through proanthocyanidins (*leucoanthocyanidins). The enzymes participating in the transformation of the proanthocyanidins to the A. have not yet been identified. However, it is assumed that hydroxylation at C-2, catalyzed by a dioxygenase, and subsequent dehydratase reactions give the flavylium structure. The hydroxylation reaction has been confirmed by molecular genetic studies. The glycosidations of anthocyanidins are catalyzed by specific nucleotide sugar-dependent glycosyltransferases. In glucosidation reactions UDP-glucose serves as glycosyl donor. In acylation reactions coenzyme A thioesters of aliphatic and aromatic acids are accepted. In esterification reactions with hydroxycinnamic acids the corresponding 1-O-acylglucosides can serve as acyl donors 4, as has been demonstrated for numerous other acylation reactions 5,6.

Lit.: 1Can. J. Chem. 68, 775 (1990). 2Zechmeister 52, 113. 3Biochem. J. 25, 1687 (1931). 4Planta 186, 582 (1992). 5Harborne & Lea (eds.), Methods in Plant Biochemistry, vol. 9, p. 45–97, London: Academic Press 1993. 6Bot. Acta 105, 146 (1992).
gen.: Harborne (1994), p. 1–22, 499-535, 565–588 ■ J. Chem. Soc., Perkin Trans. 1 1996, 735 (A. in wine) ■ Markakis (ed.), Anthocyanins as Food Colors, New York: Academic Press 1982 (use as food colorants) ■Zechmeister 52, 113-158.

Anthracyclines.

Name for highly active antibiotic and cytostatic O-glycosides from which, upon hydrolysis, the linear anellated tetracyclic anthraquinone derivative, anthracyclinone, is formed. The basic skeleton, a *polyketide, can be changed in several positions (see arrows in the formula). A. are only formed by * actinomycetes, about 200 representatives have been isolated and described, including the clinically used antitumor agents *adriamycin, *daunorubicin, and *aclarubicin. The activity of A. results from their ability to insert the planar chromophore part (rings A, B, and C) between two base pairs of the DNA double helix (intercalation) while the D ring and the sugar units hold the molecule in this position. The consequences are an inhibition of DNA and RNA polymerases as well as topoisomerase II.

Lit.: Angew. Chem. Int. Ed. Engl. 25, 790 (1986) (synthesis) ■ El Khadem (ed.), Anthracycline Antibiotics, New York: Academic Press 1982 ■ Hutchinson, in: Vining & Stuttard (eds.), Genetics and Biochemistry of Antibiotic Production, p. 331–357, Boston: Butterworth-Heinemann 1995 ■ Lown (ed.), Anthracycline and Anthracenedione-based Anticancer Agents, Amsterdam: Elsevier 1988 ■ Priebe (ed.), Anthracycline Antibiotics, ACS Sympos. Ser. 574, Washington: ACS 1995 ■ Zechmeister 21, 121-182. – [HS294130; 294190]

Anthracyclinone see rhodomycins.

Anthramycins.

Table: Data of Anthramycins.

Pyrrolo [2,1 -c] [1,4] benzodiazepine antibiotics with antitumor activity from Streptomyces species. The main representative of the group is anthramycin: pale yellow prisms, soluble in hot methanol and water, epimerizes in solution, active against Gram-positive bacteria and tumors, DNA complexing activity. A. are produced by Streptomyces refuineus and S. spadicogriseus, for isolation, see Lit. 1 biosynthesis, see Lit.2, synthesis, see Lit. 3 total synthesis, see Lit.4; for abbey micin, see Lit.5, tomaymycin, see Lit.6

Lit.: 1 J. Am. Chem. Soc. 87, 5791 (1968). 2Tetrahedron Lett. 1976, 1419. 3J. Chem. Soc., Chem. Commun. 1982, 741. 4J. Am. Chem. Soc. Ill, 5417–5424 (1989). 5 J. Antibiot. 40, 145 (1987). 6J. Am. Chem. Soc. 110, 2992 (1988).
gen.: Foye, Cancer Chemotherapeutic Agents, ACS Professional Reference Book, Washington DC 1995 ■ J. Antibiot. 30, 349 (1997) -J. Org. Chem. 53, 482–487 (1988) ■ Pharm. Res. 1984, 52.- [HS 294190]

Anthranilic acid (2-aminobenzoic acid).

C7H7NO2, MR 137.14. Colorless to pale yellow, bluefluorescing, sweet-tasting plates, D. 1.412, mp. 146–147°C, pKa1 1.97, pKa2 4.79 (25°C), sublimes without decomposition; soluble in water,...