Shikimic acid biosynthetic

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. 

Flavonoids are coloured substances and occur as pigments in plants. The chemical structure is built from an acetate-derived component and a segment from the shikimic acid biosynthetic pathway. Knowledge of the... 

Danishefsky and Hirama have published a neat total synthesis of the disodium salt of prephenic acid (24), a central intermediate in the shikimic acid biosynthetic pathway.The key step involves a Diels-Alder reaction between the diene (22) and the unsaturated lactone (23). A crucial feature of this synthesis is the simultaneous protection of both the C-lO-carboxy and C-8-keto functions as a methoxy-lactone, allowing umasking in a single step by alkaline hydrolysis. 

Vitamins are classified by their solubiUty characteristics iato fat-soluble and water-soluble groups. The fat-soluble vitamins A, E, and K result from the isoprenoid biosynthetic pathway. Vitamin A is derived by enzymic cleavage of the symmetrical C q beta-carotene, also known as pro-vitamin A. Vitamins E and K result from condensations of phytyldiphosphate (C2q) with aromatic components derived from shikimic acid. Vitamin D results from photochemical ring opening of 7-dehydrocholesterol, itself derived from squalene (C q). 

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

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

Specific Control of Phytoalexin Accumulation by "Metabolite Shunting" of Biosynthetic Pathways. Graham and coworkers (personal communication), at the Monsanto Laboratories, St. Louis, have developed techniques to selectively shunt defensive metabolites, particularly of the shikimic acid cycle. Through various techniques, certain compounds are applied to plant aerial or root parts, and these compounds have the property of inducing specific accumulations of secondary metabolites. The directions of these accumulations are under known enzymic control (48), and the regulation of these enzymes is achieved by selecting appropriate inducers. Such inducers seem to provide a novel approach to the control of insects by magnifying the ability of plants to produce and concentrate antiherbivory compounds. 

In higher plants, anthraquinones are biosynthesized either via acylpolyma-lonate (as in the plants of the families Polygonaceae and Rhamnaceae) or via shikimic acid pathways (as in the plants of the families Rubiaceae and Gesneriaceae) as presented in the following biosynthetic schemes. 

The mutants that grew in the presence of shikimic acid evidently had the biosynthetic pathway blocked... 

Isoprenoid structures for carotenoids, phytol, and other terpenes start biosynthetically from acetyl coenzyme A (89) with successive additions giving mevalonate, isopentyl pyrophosphate, geranyl pyrophosphate, farnesyl pyrophosphate (from which squalene and steroids arise), with further build-up to geranyl geranyl pyrophosphate, ultimately to a- and /3-carotenes, lutein, and violaxanthin and related compounds. Aromatic hydrocarbon nuclei are biosynthesized in many instances by the shikimic acid pathway (90). More complex polycyclic aromatic compounds are synthesized by other pathways in which naphthalene dimerization is an important step (91). 

In Scheme 1.2 one possible retrosynthetic analysis of the unnatural enantiomer of shikimic acid, a major biosynthetic precursor of aromatic a-amino acids, is sketched. Because cis dihydroxylations can be performed with high diastereoselectiv-ity and yield, this step might be placed at the end of a synthesis, what leads to a cyclohexadienoic acid derivative as an intermediate. Chemoselective dihydroxylation of this compound should be possible, because the double bond to be oxidized is less strongly deactivated than the double bond directly bound to the (electron-withdrawing) carboxyl group. 

Scheme 10. Possible biosynthetic routes leading from the shikimic acid pathway to betalains and the coexisting flavonoids (excluding anthocyanins) in betalain-bearing members of the Caryophyl-lales.

Figure 4 Biosynthetic access to chorismic and shikimic acids.

Figure 7 Biosynthesis of aromatic amino acids and products derived from phenylalanine or from intermediates of the shikimate pathway. Biosynthetically equivalent positions are indicated by colored bars. The atoms indicated by the blue bars are equivalent to atoms from phosphoenol pyruvate precursor followed by the loss of one carbon atom by decarboxylation.

Davis concluded that shikimic acid was a common precursor of phenylalanine, tyrosine, tryptophan, p-aminobenzoic acid, p-hydroxybenzoic acid, and an unknown sixth factor, and he next set out to determine other substances lying on the biosynthetic pathway. The various mutants were therefore tested for syntrophism, i.e., for the ability of one mutant to produce a substance necessary for the growth of another mutant. There was thus found a thermolabile substance, X, which was a true precursor of shikimic acid (184). X was isolated from culture filtrates and identified as 5-dehydroshikimic acid (744). Similar experiments revealed a substance, W, which was a true precursor of substance X (187, 193). This also was isolated and shown to be 5-dehydroquinic acid (906). The enzyme, named 5-dehydroquinase, converting dehydroquinic acid to dehydroshikimic acid has been partially purified (606). It is fairly stable, has a high specificity, appears to have no cofactors, and is of wide occurrence in bacteria, algae, yeasts, and plants but, as expected, could not be found in mammalian liver. 

From carbohydrate precursors there is another biosynthetic pathway to shikimic acid and further to gallic acid and tannins. Shikimic acid is the starting material, via chorismic acid (formed by reaction with a second molecule of pyruvic acid) which gives rise to aromatic, i.e. phenolic, amino acids. 

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/ ... 

Futhermore C. R. Johnson et al. synthesized (-)-shikimic acid 21, the biosynthetic precursor of the benzene moiety of aromatic amino acids12 201. 

Zasshi 81, 515 (I960). C.A. 56, 470a (1962). Biosynthetic studies on incorporation of shikimic acid, q.v. into iodinin ... 

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