Chorismate acids

Animals caimot synthesize the naphthoquinone ring of vitamin K, but necessary quantities are obtained by ingestion and from manufacture by intestinal flora. In plants and bacteria, the desired naphthoquinone ring is synthesized from 2-oxoglutaric acid (12) and shikimic acid (13) (71,72). Chorismic acid (14) reacts with a putative succinic semialdehyde TPP anion to form o-succinyl benzoic acid (73,74). In a second step, ortho-succmY benzoic acid is converted to the key intermediate, l,4-dihydroxy-2-naphthoic acid. Prenylation with phytyl pyrophosphate is followed by decarboxylation and methylation to complete the biosynthesis (75). 

Phenazines — The phenazines are biosynthesized by the shikimic acid pathway, through the intermediate chorismic acid. The process was studied using different strains of Pseudomonas species, the major producers of phenazines. The best-known phenazine, pyocyanine, seems to be produced from the intermediate phenazine-1-carboxylic acid (PCA). Although intensive biochemical studies were done, not all the details and the intermediates of conversion of chorismic acid to PCA are known. In the first step, PCA is N-methylated by a SAM-dependent methyltransferase. The second step is a hydroxylative decarboxylation catalyzed by a flavoprotein monooxygenase dependent on NADH. PCA is also the precursor of phenazine-1-carboxamide and 1-hydroxyphenazine from Pseudomonas species. - - ... 

The enzyme chorismate mutase was found to accelerate the Claisen rearrangement of chorismic acid.147 For many years, the origin of the acceleration perplexed and intrigued chemists and biochemists. Polar... 

It is interesting to note that the dihydroxybenzoyl nucleus arises from chorismic acid which, in turn, is derived from erythrose phosphate and phosphoenol pyruvate, both of these substances being intermediates in the anaerobic metabolism of carbohydrate (74). Accordingly, the biogenesis of the catechol type ligand is independent of the presence of oxygen gas. 

Table 1 Kinetic and thermodynamic parameters for the spontaneous, enzyme-catalysed and antibody-catalysed conversion of chorismic acid [23] into prephenic acid [24],...

Claisen rearrangement chorismic acid to prephenic acid... 

Thus, 16 was converted via 17 and 18 into tran.i-diol derivative 19, a known synthetic precursor of ( )-chorismic acid 1. 

Wood, H. B. Ganem, B. Short Chemical Synthesis of (-)-Chorismic Acid from (-)-Shikimic Acid, J. Am. Chem. Soc. 1990,112, 8907. 

Chemical properties appropriate to a compound found at a branch point of metabolism are displayed by chorismic acid. Simply warming the compound in acidic aqueous solution yields a mixture of prephen-ate and para-hydroxybenzoate (corresponding to reactions h and l of Fig. 25-1). Note that the latter reaction is a simple elimination of the enolate anion of pyruvate. As indicated in Fig. 25-1, these reactions correspond to only two of several metabolic reactions of the chorismate ion. In E. coli the formation of phe-nylpyruvate (steps h and i, Fig. 25-1) is catalyzed by a single protein molecule with two distinctly different enzymatic activities chorismate mutase and prephenate dehydratase.34-36 However, in some organisms the enzymes are separate.37 Both of the reactions catalyzed by these enzymes also occur spontaneously upon warming chorismic acid in acidic solution. The chorismate mutase reaction, which is unique in its mechanism,373 is discussed in Box 9-E. Stereochemical studies indicate that the formation of phenylpyruvate in Fig. 25-1, step z, occurs via a... 

The flavonoids, which comprise the largest group of these natural products, are derived from a mixed acetate-shikimate pathway. A shikimate-derived C6-C3 unit combines with a six-carbon polyketide chain to provide the open-chain precursor (685) of the group. The derivation of p-hydroxycinnamic add (p-coumaric acid), the C6-C3 component, from shikimic acid proceeds through chorismic acid, prephenic acid and phenylalanine. 

Insertion into an O—H bond is generally favored over cyclopropanation, and consequently protection of hydroxy functionality is normally required. The ease of O—H insertion is nicely illustrated in a recent synthesis of chorismic acid derivatives, where the alkene functionality in (20) was totally unaffected by the carbenoid (Scheme 4).48... 

Until pyruvates. In connection with a synthesis of chorismic acid (1) McGowan and Hcrchiold1 developed a new synthesis of cnol pyruvates, as outlined in chart (I). 

A thoroughly investigated reaction on the biosynthetic pathway to aromatics is the [3+3]-sigmatropic Claisen rearrangement from chorismic acid to prephenic acid (Figure 18.8). 

A very important branchpoint compound in the shikimate pathway is chorismic acid (Figure 4.3), which has incorporated a further molecule of PEP as an enol ether side-chain. PEP combines with shikimic acid 3-phosphate produced in a... 

Returning to the main course of the shikimate pathway, a singular rearrangement process occurs transforming chorismic acid into prephenic acid... 

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