Chorismic acid derivatives

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... 

Use of Mutants in Biosynthetic Studies Formation of Chorismic Acid Derivatives of Chorismic Acid Biosynthesis of Tryptophan Indole 3-Acetic Acid Avenalumins from Oats DIMBOA and Related Compounds Biosynthesis of Phenylalanine and Tyrosine Compounds Derived from Shikimic Pathway Intermediates... 

Chorismic acid derivatives Chloramphenicol (D 8.2) Affecting mRNA translation... 

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. 

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

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. 

Figure 4.11). This reaction, a Claisen rearrangement, transfers the PEP-derived side-chain so that it becomes directly bonded to the carbocycle, and so builds up the basic carbon skeleton of phenylalanine and tyrosine. The reaction is catalysed in nature by the enzyme chorismate mutase, and, although it can also occur thermally, the rate increases some 106-fold in the presence of the enzyme. The enzyme achieves this by binding the pseudoaxial conformer of chorismic acid, allowing a transition state with chairlike geometry to develop. 

The quinone ring is derived from isochorismic acid, formed by isomerization of chorismic acid, an intermediate in the shikirnic acid pathway for synthesis of the aromatic amino acids. The first intermediate unique to menaquinone formation is o-succinyl benzoate, which is formed by a thiamin pyrophosphate-dependent condensation between 2-oxoglutarate and chorismic acid. The reaction catalyzed by o-succinylbenzoate synthetase is a complex one, involving initially the formation of the succinic semialdehyde-thiamin diphosphate complex by decarboxylation of 2-oxoglutarate, then addition of the succinyl moiety to isochorismate, followed by removal of the pyruvoyl side chain and the hydroxyl group of isochorismate. 

The reaction in the shikimic acid pathway is, of course, the [3,3]-sigmatropic shift in which chorismic acid rearranges to prephenic acid on the way to aromatic rings (p. 1403). The simpler reaction given here is one of the family of reactions from Chapter 36 (pp. 944-6) using an allylic alcohol and an enol derivative of a carbonyl compound. In this case we have the enol ether of a ketone. We must combine these to make an allyl vinyl ether for rearrangement. 

In cell cultures of Catharanthus roseus 2,3-DHBA was found to be produced after elicitation of the cells with fungal cell-wall preparations [40,41]. The production of this compound in cell cultures was paralleled by an increase in the activity of the enzyme isochorismate synthase [40]. Although direct evidence for the intermediacy of iso-chorismate is not yet reported, it seems that the isochorismate biosynthetic pathway for benzoic acid derivatives can also be found in plants. 

The naturally occurring naphthoquinones such as lawsone and juglone are products of the shikimic acid pathway to aromatic amino-acids but the path which leads to these naphthoquinones branches from the main pathway before the formation of aromatic compounds, probably no later than chorismic acid.It will be most interesting to see whether the biosynthesis of shihunine also follows this route all the other bases of plant origin which arise from products of the shikimic acid pathway derive from aromatic precursors. 

In this review we have only dealt with alkaloid biosynthesis in C. roseus the biochemistry of this plant has also been studied in detail for other aspects, such as anthocyanin production, phosphate metabolism, cell growth, and cell division cycle (e.g., ref. 362). Unfortunately, most of the studies concerning the primary metabolism are not linked with those of secondary metabolism. However, one may expect that in the future the studies on secondary metabolism, such as chorismate-derived products (an-thocyanins, benzoic acid derivatives, and alkaloids) and terpenoid-derived products such as the alkaloids, will be integrated. This will eventually allow us a much better insight into the overall biochemistry of the plant. All of the available information makes C. roseus an outstanding model system for the study of the regulation of plant metabolism. 

Biosynthesis Like other aromatic amino acids, e.g., Phe and Tyr, Trp is formed on the shikimic acid pathway. There is a branching point at chorismic acid one branch leads to Phe and Tyr, the other to Trp choris-mic acid - anthranilic acid (anthranilic acid synthase, EC 4.1.3.27)- A-(5 -0-phosphoribosyl)-anthranilic acid (anthranilic acid phosphoribosyl transferase, EC 2.4.2.18)- 1 -o-carboxyphenylamino-1 -deoxyribu-lose 5-phosphate [A-(5 -phosphoribosyl)anthranilic acid isomerase]- indole-3-glycerol phosphate (in-dole-3-glycerol phosphate synthase, EC 4.1.1.48) - indole (tryptophan synthase, EC 4.2.1,20)+serine - Trp. Many biologically active indole compounds are derived from Trp, e. g., 5-hydroxytryptophan, 5-hydroxy-tryptamine ( serotonin), and melatonin as well as many indole alkaloids. 

Both phenylalanine and tyrosine are derived from chorismic acid, which is itself derived from shikimic acid-3-phosphate through the shikimic acid pathway. In this sequence, chorismic acid is first transformed into prephenic acid by chorismate mutase. If prephenic acid is converted into phenylpyruvic acid by... 

Anthranilic acid, which is derived from chorismic acid, is a nonessential amino acid. 

On the other hand, chorismic acid, which is derived from shikimic acid, is also a precursor of phenylalanine and tyrosine, which are essential amino acids [1]. Among the alkaloids, there is a group derived specifically from anthranilic acid, and this chapter presents some of these alkaloids. 

The biosynthesis of compounds derived from shikimic acid is closely linked to that of isomers of vitamin K (35) (Fig. 6.7). In plants and in microorganisms, die aromatic ring is formed via the shikimate pathway, which does not exist in animals. Only recently has it been established that vitamin K synthesis branches from wo-chorismic acid (36) and not from chorismic acid (37). fro-Chorismic acid (36) is derived from shikimic acid (see Chapter 7) (Leistner, 1986). Both of the cyclization steps leading to naphthoquinones and vitamin K are unusual in plants. 

Derivatives of wo-Chorismic Acid Arbutin and Hydroquinones References... 

Tryptophan is an essential amino acid for most organisms. In plants and bacteria, this compound is derived from chorismic acid. Many groups of secondary compounds are formed from tryptophan among these are several simple amine derivatives and a number of alkaloids. 

The first step in the formation of tryptophan involves conversion of chorismate (9) to anthranilate (11) (Fig. 7.4). Although the reaction is not well understood, it is catalyzed by the enzyme anthranilate synthase and utilizes L-gluta-mine. By means of specifically labeled chorismic acid, it was determined that the protonation involved in the formation of anthranilic acid had occurred from the re face (Figure 4) (Floss, 1986). Anthranilic acid (11) also serves as an intermediate for the synthesis of a number of secondary compounds and occurs free and as various derivatives in many plants and other organisms (Dewick, 1989). 

Another series of compounds that appear to be derived from ijo-chorismic acid are cyclohexene oxides such as cro-tepoxide (36), senepoxide (37), and pipoxide (38) from Croton macrostachys (Euphorbiacee), Uvaria zeylanica (An-nonaceae), and Piper hookeri (Piperaceae), respectively (Fig. 7.13). These compounds have demonstrated antitumor activity (Jolad et al., 1981). 

In some fungi, salicylic acid (65) and related compounds, such as 6-methylsalicylic acid, are derived from acetate-ma-lonate pathways. In bacterial systems, similar compounds are derived from chorismic acid via isochorismic acid see Chapter 7). Salicylic acid often is found in species of Salix... 

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