Biosynthesis and Metabolism of Anthraquinone Derivatives Dmitry Yu. Korulkin, Raissa A. Muzychkina obtain all necessary aromatic compounds from food, Abstract—In review the generalized data about biosynthetic routs medicines, and vitamins. formation anthraquinone molecules in natural cells. The basic Various natural quinones: benzo-, naphtho-, benzanthreno- possibilities of various ways of biosynthesis of different quinoid phenanthreno-, and anthraquinones, anthracyclinones, and substances are shown. fused and other quinones also belong to the group of aromatic substances of the secondary origin. Keywords—anthraquinones, biochemical evolution, biosynthesis, Of the quinones listed above, 9,10-anthraquinones are the metabolism. most important in the life of plants. They occur in lower I. INTRODUCTION plants, algae, fungi, lichens, mosses, and ferns. In higher plants, the quinones are encountered in the form of N elucidating the course of biochemical evolution, it has polyhydroxy derivatives and are found in all parts of woody I been shown that the biosynthesis of the same substances in plants and bushes. plants and animals occurs in much the same way. This is There is no consensus of opinion on the role of anthracene manifested, most of all, in similar compositions of the primary derivatives in plants, but it was established that, for example, metabolites, i.e., vitally important compounds: proteins, hydroxymethyl anthraquinones protect plants against parasites nucleic acids, fats, carbohydrates, and some intermediate and protect seeds against birds, promote accumulation of compounds of their biosynthesis. polysaccharides, and take part in redox processes. An enormous number of other natural compounds, All the hypotheses about the origin and formation of including quinones, are secondary metabolites, but this does phenolic compounds and, in particular, hydroxyanthra- not mean that these substances are insignificant or useless for quinones in plants reduce to the following five schemes: the life of plants. 1) biosynthesis of aromatic nuclei proceeds simultaneously Secondary metabolites have played and are playing a great with the photosynthesis from precursors of saccharides; role in the survival of separate plant species during the 2) phenols are formed through condensation of bioses and progress of evolution and in the interaction of plants with the trioses with other products of saccharide decomposition; environment. Thus, the appearance of the polymer lignin at 3) phenols are produced directly from hexoses; early stages of the life on the Earth allowed water plants to 4) the biosynthesis of phenols occurs via acetic acid; migrate to land and occupy it; the living nature owes the 5) phenols are obtained from hexoses or aminoacids through abundance of colours to the pigments of the phenolic type, in shikimic acid [1]. particular, to anthocyans; the protective reactions against In 1907 Colly proposed and then experimentally confirmed mechanical injuries or microorganism attacks are also the possibility of obtaining aromatic substances from associated with the secondary substances - quinones. Various polyacetic acids by virtue of a «head-to-tail» type quinones provide for the process of respiration and the condensation. division, growth, and development of cells. Later, Birch and Donovan have shown that some other natural products can also be formed in this way, the II. RESULTS AND DISCUSSION cyclization being possible either at carbon atoms 1-6 to give The biosynthesis of various substances of the secondary ketones with a phloroglucinol ring or at carbon atoms 2-7 to origin, along with the photosynthesis, is one of the give acids. To explain the absence of some OH groups, the characteristic features of plant organisms. Only plants and suggestion was made that, prior to cyclizing; the molecules of microorganisms are capable of synthesizing substances with polyacetic acids may be partially reduced. Whereas Colly has aromatic structures. Animals do not possess this property; they synthesized phenolic compounds from acetic acid, Birch has succeeded in obtaining the first experimental data supporting the acetate theory in relation to Penicillium griseofulvum F. A. Author is with the Department Chemistry and Chemical Technology, cultures [2]. al-Farabi Kazakh National University, Almaty, CO 050040 Kazakhstan In 1935 Fischer elucidated the role of shikimic and quinic (corresponding author to provide phone: 727-387-1751; fax: 727-292-3731; e- acids in the formation of gallic acid. In W. Margn’s opinion, mail: e-mail: [email protected]). S. B. Author is with the Department Chemistry and Chemical Technology, the shikimate pathway implies the participation of L- al-Farabi Kazakh National University, Almaty, CO 050040 Kazakhstan (e- phenylalanine in the biosynthesis of phenolic compounds. mail: [email protected]). In spite of the common nature of the biosyntheses of The structural modifications that occur after the formation phenols, different plants can produce the same compounds of an aromatic skeleton include O-methylation, oxidation, through different biosynthetic pathways. It is not accidental hydroxylation, dimerization, glycosidation, etc, which can that, along with simple amino acids and carbohydrates, the proceed in various combinations, both consecutively and majority of plants contain phenols, phenolic acids, flavonoids, simultaneously. naphthoquinones, and anthraquinones. The number of the About half of the anthraquinone compounds in higher plants individual compounds, whose biosynthetic pathway can be have substituents in one of the benzene rings, some of them regarded as proven, constitutes only a small portion of known are devoid of a side carbon chain (for example, alizarin) or natural compounds with established structures. hydroxy groups (for example, 2-methylanthraquinone). The Since the anthraquinones are oxidized aromatic compounds, majority of such compounds have been found in plants of the it would make sense to assume that their biosynthesis is Rubiaceae, Bignoniaceae, and Verbinaceae families; in the similar to that of other aromatic structures - phenols, phenolic latter two families, anthraquinones and naphthoquinones are acids, benzo- and naphthoquinones, catechols, flavonoids, represented virtually equally. The production of non- chalcones, aromatic amino acids, and so on. substituted anthraquinone in the Quebrachia lorentzii, many According to numerous studies [3,4], the origin of naphtha- Acacia species of the Leguminosae family, and in the tobacco quinones and anthraquinones, unlike that of, for instance, leaves as well as the formation of 10,10’-bianthrone in the hydroxycinnamic acids, coumarins, and flavonoids, is based Ustilago Zeal culture are the least understood [9]. on several biosynthetic pathways. This accounts for the variety Analysis of the structural variety of the anthracene of structures of natural anthraquinones. As a rule, to produce glycosides isolated at different stages of plant growth has the main structure, only one (the principal) biosynthetic shown that the О-addition of a carbohydrate substituent is pathway is realized, while related compounds are formed characteristic of the glycosided forms of anthraquinones, during subsequent transformations of the main structure. while the С-addition is a distinctive property of anthrones and According to E. Leistner’s classification [5], the following dianthrones. This points to a single predominant pathway of biosynthetic pathways are possible: acetate-malonate route; their biosynthesis, although O- and C-glycoside bonds can from L-tyrosine via toluhydroquinone; from L-phenylalanine sometimes be found simultaneously in the same plant and via trans-cinnamic, p-coumarinic, and p-hydroxybenzoic even in the structure of a single compound, for example, in acids; via shikimic, isochorismic, and o-succinylbenzoic acids; cascaroside A, which is a 8--D-glucopyranosyloxy-10--D- via mevalonic acid. glucopyranoside of aloe-emodin-9-anthrone. The first and the fourth biosynthetic pathways have been As a rule, a freshly gathered plant material contains a small confirmed experimentally; however, virtually all the above- amount of aglycones, which increases upon drying and tissue mentioned compounds have been detected among the destruction, because the glycosides or the reduced forms of intermediates, which suggests that a combination of several glycosides present in tissues in vivo are easily cleaved to principal pathways is realized. sugars and the corresponding aglycones, indicating that two According to the acetate theory developed by Colly, Birch, pathways predominate in the biosynthesis of anthracene and Donovan [6], which has been accepted as the most glycosides. probable hypothesis, the acetic acid in plants undergoes Naptho- and anthraquinones differ from other secondary condensation giving a polyketomethylene chain. metabolites in that they are accumulated in significant The polyketomethylene chain may also be produced by quantities in suspension cultures and callus tissues of plants, condensation of acetate and malonate fragments. for example, in a suspension cell culture of bedstraws, in The resulting polyketide chain can bend in different ways, callus tissues of catalpa, puccoon, foxglove, and so on, depending on the number of-CH2-CO units, with the anthraquinones being sometimes found only in suspension cell subsequent cyclization or aromatization. The simplest way of cultures and callus tissues but not in the plant itself or its cyclization