Aromatic acids synthesis

Herbicides also inhibit 5- (9/-pymvylshikiniate synthase, a susceptible en2yme in the pathway to the aromatic amino acids, phenylalanine, tyrosine and tryptophan, and to the phenylpropanes. Acetolactate synthase, or acetohydroxy acid synthase, a key en2yme in the synthesis of the branched-chain amino acids isoleucine and valine, is also sensitive to some herbicides. Glyphosate (26), the sulfonylureas (136), and the imida2oles (137) all inhibit specific en2ymes in amino acid synthesis pathways. 

Antibiotic A201A. Antibiotic A201A (23), produced by S. capreolus is an /V -dimethyladenine nucleoside stmcturaHy similar to puromycin (19). Compound (23) which contains an aromatic acid and monosaccharide residues (1,4), inhibits the incorporation of amino acids into proteins but has no effect on RNA or DNA synthesis. Compound (23) does not accept polypeptides as does (19), and does appear to block formation of the initiation complex of the SOS subunit. It may block formation of a puromycin-reactive ribosome. 

Flavone formation is believed to proceed through a similar mechanism as the synthesis of chromones, albeit aromatic acid anhydrides and their corresponding salts are used. The first step is benzoylation of 12 to give the ester 14. Enolization and o-alkylation then affords the enolbenzoate 15. Enolbenzoate 15 then undergoes an acyl transfer to yield... 

The use of silylated monomers is an interesting alternative method of aromatic polyester synthesis since the silylated gaseous by-products cannot participate in the reverse reaction, shifting polyesterification toward polymer formation. Reactions between silyl esters and acetates (Scheme 2.23) and reactions between silyl ethers and acid chlorides (Scheme 2.24) have been applied to the synthesis of linear265-267 and hyperbranched wholly aromatic polyesters202,268 269 (see Section 2.4.5.2.2). 

Glyphosate also inhibits the activity of a form of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (13), however, this inhibition is relatively weak. Effects of glyphosate on the enzymes of aromatic amino acid synthesis have been described in more detail in recent reviews (14-17). 

The present procedure4 is an especially effective method for the synthesis of esters of aromatic acids and hindered tertiary alcohols or of acid-labile alcohols such as 2,2-diphenylethanol. The yields are excellent, and the reaction procedure is simple. The method is illustrated by the preparation of /-butyl p-toluate, a compound that could not be prepared by a conventional method0 of esterification involving the acid chloride and /-butanol in the presence of dimothylaniline. Examples of esters prepared by this method are illustrated in Table I. 

Figure 3.5 The synthesis of diazepam is initiated by the double acylation of an aromatic amine with an aromatic acid chloride. A second equivalent of the p-chloroaniline leads to a six-membered ring with two nitrogens. This is hydrolytically opened to expose a free amino group which reacts with an aminoester to yield a seven-member ring. The amide nitrogen is then methylated.

Alkylation of the enolate of a carboxylic acid, formed as an intermediate in the Birch reduction of an aromatic acid, has been successfully exploited in synthesis, e.g., in the synthesis of gibberellic acid. A model compound 24 was reduced with sodium in diethyl ether-liquid ammonia and the resulting carbanion was alkylated with iodomethane to give 25 in ca. 80% yield87. 

Figure 2.9 Part of the biosynthetic pathway of aromatic amino acid synthesis...

Carboxylic acids can be alkylated in the a position by conversion of their salts to dianions [which actually have the enolate structures RCH=C(0 )21497] by treatment with a strong base such as lithium diisopropylamide.1498 The use of Li as the counterion is important, because it increases the solubility of the dianionic salt. The reaction has been applied1499 to primary alkyl, allylic, and benzylic halides, and to carboxylic acids of the form RCHjCOOH and RR"CHCOOH.1454 This method, which is an example of the alkylation of a dianion at its more nucleophilic position (see p. 368), is an alternative to the malonic ester synthesis (0-94) as a means of preparing carboxylic acids and has the advantage that acids of the form RR R"CCOOH can also be prepared. In a related reaction, methylated aromatic acids can be alkylated at the methyl group by a similar procedure.1500... 

FIGURE 18-14 Treatment for deficiencies in urea cycle enzymes. The aromatic acids benzoate and phenylbutyrate, administered in the diet, are metabolized and combine with glycine and glutamine, respectively. The products are excreted in the urine. Subsequent synthesis of glycine and glutamine to replenish the pool of these intermediates removes ammonia from the bloodstream. 

The reaction is illustrated by the formation of propiophenone from diphenyl-cadmium and propanoyl chloride (Expt 6.126). Better yields are obtained by carrying out the synthesis in this manner rather than attempting the alternative combination of diethylcadmium with benzoyl chloride. Alternatively an alkyl-lithium cuprate could be used with an aromatic acid chloride (p. 616). 

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