Shikimic acid-derived phenols

The effects of this inhibitor on the metabolism of A. fumigatus were very different from those of the other compounds used, since formation of all the characteristic acetate-derived phenols was strongly suppressed (Packter and Collins, 1974). Treatment of cultures gave a completely altered pattern and led unexpectedly to the secretion of atypical shikimic acid-derived phenols, including 2,3-dihydroxybenzoic acid, 4-hydroxyphenylpyruvic acid, and 4-hydroxybenzyl cyanide. In addition, the inhibitor was metabolized directly by transamination to fluorophenylpyruvic acid. 

Benzene compounds. Benzene compounds are an important group in varietal aroma, abimdant in wines, including aromatic alcohols, aldehydes, volatile phenols and shikimic acid derivates. The volatile phenols in wines can come from grapes, both as free and bound aroma, or be generated during the alcoholic fermentation by chemical reactions such as phenolic add degradation, or in the case of vinylphenols due to brettanomyces contamination (Suarez et al., 2007). Volatile phenols are considered characteristic components of wine aroma, although their influence on the final product may be positive or... 

Two major groups of phenols exist that are formed by the sequential addition of C2 units to a growing chain. Acetyl-CoA is generally used as the primer in fungal systems, whereas a shikimic acid-derived acyl-CoA is required for flavonoid synthesis in higher plants. Flavonoids are multiringed phenols found most commonly in flowers and fruit, where they are responsible for the color. 

Formation of esters by reaction of diazoalkanes with carboxylic acids is a mild and often quantitative procedure. It is particularly useful for the preparation of methyl and ethyl [4], benzyl [3, 58], and benzhydryl esters [45, 59, 60], although not on a large scale. The reaction is initiated by proton transfer from the carboxyl group and 0-alkylation is a competing reaction with phenolic acids. Diazoalkanes may also add to carbonyl [61] and olefinic linkages [62]. Thus the shikimic acid derivative (16) with a limited amount of diazomethane at low temperature gives the methyl ester (17) but with an excess of the reagent forms the isomeric pyrazolines (18 and 19) [63, 64]. 

Figure 1. Biosynthetic pathway for production of shikimic acid pathway-derived phenolic compounds in higher plants.

In contrast to the rutelines, the melolonthine scarabs generally use terpenoid-and amino acid-derived pheromones (reviewed in Leal, 1999). For example, the female large black chafer, Holotrichia parallela Motschulsky, produces methyl (2.S, 3. Sj - 2 - am ino-3-methy lpcn tanoatc (L-isoleucine methyl ester) as an amino acid-derived sex pheromone (Leal et al., 1992 Leal, 1997). There is no direct evidence that the chafer beetles or any other Coleoptera use the shikimic acid pathway for de novo pheromone biosynthesis, but some scarabs and scolytids (see section 6.6.4.2) may convert amino acids such as tyrosine, phenylalanine, or tryptophan to aromatic pheromone components (Leal, 1997,1999). In another melolonthine species, the female grass grab beetle, Costelytra zealandica (White), the phenol sex pheromone is produced by symbiotic bacteria (Henzell and Lowe, 1970 Hoyt et al. 1971). 

Different silylating agents have been utilized for the preparation of TMS derivatives of phenolic acids and related substances. Shyluk et al. [162] used the following procedure for the GC of shikimic acid and related compounds. A 2-mg amount of the acid was dissolved in 0.5 ml of dry acetone and 0.2 ml of HMDS and 0.1 ml of TMCS were added. After shaking for 30 min the mixture was allowed to stand for 10 min and 1 /al was injected into the chromatograph. SE-30, QF-1 and XE-60 were used as stationary phases. 

Phenylpropanoids have an aromatic ring with a three-carbon substituent. Caffeic acid (308) and eugenol (309) are known examples of this class of compounds. Phenylpropanoids are formed via the shikimic acid biosynthetic pathway via phenylalanine or tyrosine with cinnamic acid as an important intermediate. Phenylpropanoids are a diverse group of secondary plant compounds and include the flavonoids (plant-derived dyes), lignin, coumarins, and many small phenolic molecules. They are known to act as feeding deterrents, contributing bitter or astringent properties to plants such as lemons and tea. 

The C-glycoside 178 was used by Boyd and Sulikowski [87] in the total synthesis of enantiomerically pure urdamycinone B (182) and 104-2 (183) making use of the diene 107 derived from shikimic acid (Scheme 29) and the NMO oxidation to generate the C-5 phenols (Scheme 40). Thus, the bromonaphthoquinone 179 (prepared by treatment of phenol 178 with NBS) formed the tetracycle 180 through a Diels-Alder reaction with the diene 107 in analogy to sugar-free reactants. Osmylation to a cis-diol, deprotection, oxidation, and acetalization gave the acetonide 181. The decisive step in the aromatization to 182 and 183 was the reaction with NMO (Scheme 46). Aromatization was also effected by direct periodane oxidation of adduct 180 to derive 182 after deprotection. 

It has been noted that the chemical diversity of plant phenolics is as vast as the plant diversity itself. Most plant phenolics are derived directly from the shikimic acid (simple benzoic acids), shikimate (phenylpropanoid) pathway, or a combination of shikimate and acetate (phenylpropanoid-acetate) pathways. Products of each of these pathways undergo additional structural elaborations that result in a vast array of plant phenolics such as simple benzoic acid and ciimamic acid derivatives, monolig-nols, lignans and lignin, phenylpropenes, coumarins, stilbenes, flavonoids, anthocyanidins, and isollavonoids. 

Shikimic acid (64) is the biosynthetic precursor to an array of aromatic compounds, including benzoic and cinnamic acids/ This pathway is utilized by microorganisms and plants, but not by animals, which obtain essential shikimate building blocks like phenylalanine from their diets/ Red algae are known to be a prolific source of halogenated phenolic metabolites derived from shikimic acid, comprising approximately 5% of known algal metabolites/ ... 

Benzoic and cinnamic acid derivatives and flavonoids are the two most distributed phenolics within plants. Polyphenolic units are biosynthesized via shikimate pathway, resulting in cinnamic acids C -C phenylpropanoid building block that also contributes to other plant phenolics backbones such as those from flavonoids (Q-Ca-Ce), anthocyanidins (C6-C3-C6), and coumarins (C6-C3). Stilbeneoids (C6-C2-C6) and benzoic acid derivatives (Cfi-Ci) such as gallic and ellagic acids are also synthesized through this metabolic pathway (Fig. 1). 

Most aromatic compounds in plants are derived from shikimic acid metabolism many of these substances are phenols. Compounds derived from this pathway are extensively modified and considered under other classes of plant secondary metabolites. Although many types of secondary compounds are produced from intermediates of the shikimic acid pathway (e.g., certain naphthoquinones and anthraquinones discussed in Chapter 6), most are derived from four aromatic amino acids phenylalanine, tyrosine, anthranilic acid, and tryptophan. Aromatic compounds that arise from the shikimic acid pathway usually can be distinguished from those of other origins by their substitution patterns and by a knowledge of the compounds with which they co-occur. 

Compounds derived from shikimic acid pathways and especially phenolic substances have been encountered in a number of studies of chemical interactions between plants. This chemical warfare is often called allelopathy. Although much controversy surrounds the importance of this phenomenon, allelopathy seems to be most important in seasonally dry habitats. 

A wide range of aromatic products in the plant kingdom originate from intermediates of the shikimic acid pathway. These include amino acids and ubiquinone among important primary metabolites and also many other compounds (in contrast fo fungi which possess many acetate-derived products), such as lignins, alkaloids, and phenolic acids. Flavonoids (and stilbenes) also arise in part by this route but additionally utilize acetate in the course of their biosynthesis, which will therefore be described in this chapter. 

Chrysophanol (XXIII), an anthraquinone isolated from the leaves of Rumex alpinus (Polygonaceae), is also formed from acetate (and presumably therefore derived via the acetate-malonate pathway) (Leistner and Zenk, 1969) and not, as previously considered, from shikimic acid and mevalonate. Only anthraquinones such as alizarin lacking a C-methyl group and not hy-droxylated in ring A are made in this way, despite an apparent similarity in structure thus at least two independent routes also exist for the synthesis of these compounds and reflect the diversity available for the biogenesis of multiringed phenols in plants. 

These compounds contain a benzene ring structure with an attached propane (C3) side chain (see Chapter 2). The most common precursor is cinnamic acid, a derivative of the shikimic acid pathway. They include some aldehydes, phenols and phenolic ethers. 

The multibranched shikimic acid pathway provides the intermediates for the synthesis of the three amino acids phenylalanine, tyrosine and tryptophan in microorganisms and plants. In plants, these three amino acids are precursors for a variety of secondary metabolites such as alkaloids, coumarins, flavonoids, lignin precursors, indole derivatives and numerous phenolic compounds (Fig. 1). The role of the aromatic amino acids in protein synthesis is well known as is the role of indoleacetic acid in plant development however, the function of the various secondary products is much less clear. Various physiological roles have been proposed including pest resistance, chromagens in flowers and fruits, and precursors for the structural component, lignin. 

Phenolic oxidation can be seen in a wide range of biosyntheses. In plants, propylbenzene derivatives, which are produced from shikimic acid, are enzymatically oxidized to yield lignans, neolignans, and lignins. In contrast to the dimeric structures of the former, lignins possess... 

The amino acid phenylalanine is derived from gallic acid, being this compound biosynthesized in the shikimic acid metabolic route. Most of the phenolic compounds from higher plants are also derived from this amino acid, formed in the phenylpropanoid metabolic route, in the cell cytoplasm, being various enzymes involved in this metabolism. Phenylalanine ammonia lyase interacts with phenylalanine forming cinnamic acid, that is, hydrolyzed by citmamate-4-hydroxylase, rendering p-coumaric acid. Different hydroxylations and/or methoxylations, of this... 

Phenolic compounds or polyphenols constitute one of the most abtmdant and widely distributed groups of substances in the plant kingdom with more than 8,000 phenolic structures currently known. They are products of the secondary metabolism of plants and arise biogenetically from two main primary synthetic pathways the shikimate pathway and the acetate pathway. Both acetic acid and shikimic acid are derived from glucose metabohsm [15] (Scheme 74.1). 

Lichens had to evolve diverse biosynthetic pathways to produce such complex arrays of secondary metabolites polyketide, shikimic acid, and mevalonic acid pathways. Most of the lichen substances are phenolic compounds. Polyketide-derived aromatic compounds, depsides, depsidones, dibenzofurans, xanthones, and naphthoquinones, are of great interest. Compounds from other pathways are esters, terpenes, steroids, terphenylquinones, and pulvinic acid (Fahselt 1994 Cohen and Towers 1995 Muller 2001 Brunauer et al. 2006, 2007 Stocker-Worgotter and Elix 2002 Johnson et al. 2011 Manojlovic et al. 2012). So, many lichens and lichen products have proved to be a source of important secondary metabolites for food and pharmaceutical industries (Huneck 1999 Oksanen 2006)... 

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