Acetyl anthranilic acid

Ajacine (= A-Acetyl -anthranilic acid ester of lycoctonine)... 

Acetaldehyde, Acetamide, Acetaminophen, N-Acetyl Anthranillic Acid, Alumina (activated), Aluminum Chloride, Aluminum Oxide,... 

Indonesia" Acetic anhydride, A -acetyl anthranilic acid, ephedrine, ergometrine, ergotamine, isosafrole, 3,4-methylene-dioxyphenyl-2-propanone, 1 -phenyI-2-propanone, piperonal, pseudoephedrine, safrole anthranilic acid, phenylacetic acid 18 February 2000... 

The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Most of the nonsteroidal anti-inflammatory drugs (NSAIDs) are carboxylic acids. Aspirin (8.69) (acetylsalicylic acid, ASA) has been used since the turn of the last century to reduce pain and fever, but the parent compound, salicylic acid, has been known and used since antiquity, owing to its common occurrence as a glycoside in willow bark. Acetylation merely decreases its irritating effect. Among the numerous other salicylates known and used, flufenisal (8.70) has a longer duration of activity and fewer side effects than aspirin. Mefenamic acid (8.71) and flufenamic acid (8.72) are derivatives of anthranilic acid, while ibuprofen (8.73) and naproxen (8.74) are derivatives of phenylacetic and naphthylacetic acids, respectively. 

The above procedure is essentially that of Ullmann and Bleier.2 2-Aminobenzophenone has also been prepared by reduction of 2-nitrobenzophenone,3 by the Hofmann reaction of the amide of o-benzoylbenzoic acid with sodium hypobromite,4 by the action of an excess of benzoyl chloride on aniline at 220°,6 and by hydrolysis of the acetyl derivative which is obtained by the action of phenylmagnesium bromide on 2-methyl-3,l,4-benzoxaz-4-one (from anthranilic acid and acetic anhydride).6 Various methods for the preparation of 2-aminobenzophenones have been summarized critically by Simpson, Atkinson, Schofield, and Stephenson.7... 

Amidation of N-(2-carboxyphenyl)anthranilic acid (532) gave the 2,2 -dicarbamoyldiphenylamines (533), which were then cyclized with chloro-acetyl chloride to the quinazolino[l,2-a]quinazolines (534) (81JOC1571). 

Even the sterically hindered 2,6-disubstituted aryl iodide 443 is carbonylated smoothly to give 445. Alkyl iodide present in the alcoholic component 444 remains intact under the carbonylation conditions. This carbonylation reaction is a key reaction in the synthesis of zearalenone (446) [216]. Optimal conditions for technical synthesis of the anthranilic acid derivative 448 from bromide 447 has been studied, and it has been found that A-acetyl protection of 447, which has a chelating effect, is important [217]. Cheaply available chlorides are rather inert [13]. The carbonylation of chloride 449 in the presence of DBU and Nal gives the amide 450 [218],... 

Alkaloids of Delphinium dictyocarpum N- Acetyldelectine and Demethylenedelt-amine.—Further investigations of the aerial parts of D. dictyocarpum DC. have yielded a new base (34), C26H41N08, m.pt. 116—118 °C.27 Spectral analyses (i.r., n.m.r., and mass) indicate the presence of an N-ethyl and three methoxy-groups, and an N-acetyl anthranilate ester, on a lycoctonine-type skeleton. Saponification of (34) gave anthranilic acid and a base identical with that obtained from delectine (35). Therefore, this new alkaloid was assigned the structure of N-acetyldelectine (34). 

In a bimolecular cycloaddition reaction 1-phenylbenzotriazole (369) is obtained from dehydrobenzene (by diazotization of anthranilic acid) and phenyl azide (64joc3733, 6SCB3142). The synthesis of 1-glucosylbenzotriazole from glucosyl azides and dehydrobenzene has been accomplished in this way, 5delding, for example, l-(2,3,4,6-tetra-0-acetyl-j8-D-glucopyranosyl)benzotriazole (370) (68jhc699>. 

We carried out several experiments by loading with 100 or 50 mg/kg body weight of L-tryptophan and determining kynurenine, N-a-acetyl-kynurenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, and free anthranilic acid. These tests were performed in a variety of conditions and the results are discussed in the following sections. 

Reactions of piperazine-2,5-diones with phosphorus pentachloride and phosphorus pentabromide have been described in Sections V.ID and V.IF, respectively. Aromatic aldehydes condense with 3-methylpiperazine-2,5-dione in the presence of acetic anhydride to form mainly mono-A -acetyl derivatives of trans-3-arylidene-6-methylpiperazine-2,5-diones (e.g., 96, R = Ac) (1066). In these products the acetyl group was shown to be attached to position 1 and the 4,5-amide group was found to be sterically hindered. Photolysis formed the cis isomers. Both isomers were deacetylated with methanolic potassium hydroxide (1066). Condensation of 1,4-diacetylpiperazine-2,5-diones with aldehydes has been applied to the synthesis of unsymmetrical 3,6-diarylidenepiperazine-2,5-diones and the reaction has been extended to l,4-diacetyl-3,6-dimethylpiperazine-2,5-diones (1624). Treatment of (96, R = H) with triethyloxonium tetrafluoroborate in dichloromethane gave the monoimino ether, 5-benzylidene-6-ethoxy-3-hydroxy-2-methyl-2,5-dihydropyrazine (97) (1066). l-Methylpiperazine-2,5-dione similarly treated gave 5-ethoxy-l-methyl-2-oxo-l,2,3,6-tetrahydropyrazine (which was condensed with anthranilic acid at 150° to 2-methyl-l,2-dihydropyrazino[2,l-fi]quinazoline-3(4/0.6-dione (98) (1625), and l,4-dimethylpiperazine-2,5-dione gave 5-ethoxy-l,4-dimethyl-2-oxo-1,2,3,4-tetrahydropyrazine and 5,5-diethoxy-l,4-dimethylpiperazin-2-one (1626). 

Another related reaction that goes through a ketimine is the conversion of the amino acid kynurenine to alanine and anthranilic acid. It presumably depends upon hydration of the carbonyl group prior to P cleavage (Eq. 14-35). An analogous thiolytic cleavage utilizes CoA to convert 2-amino-4-ketopentanoate to acetyl-CoA and alanine. ... 

Delectine.—A new diterpenoid alkaloid, delectine, has been isolated from Delphinium dictyocarpum7 This base, C31H44N2O8, m.p. 107—109 C, was shown to be the anthranilate ester (6) by chemical and spectral studies and by conversion into 00 -dimethyl-lycotonine (7). Acetylation of delectine gave an NO-diacetyl derivative (8). On alkaline hydrolysis of delectine, anthranilic acid and the alkamine (9) were obtained. Methylation of (9) with methyl iodide-sodium hydride gave (7), which was... 

C]Tryptophan gave inactive alkaloids but tritiated 2,4-dihydroxy-quinoline (34) and its N-methyl derivative were incorporated into (47) (0.009 % and 0.020% respectively) an early route had suggested the derivation of what was essentially (34) from tryptophan. Radioisotope dilution showed the presence of both these quinoline precursors together with iV-acetyl- and N-methyl-anthranilic acid in A. baueri. A satisfactory incorporation of N-methylanthranilic acid into (47) was found in Evodia xanthoxyloides, and this, together with its natural occurrence, indicates that early methylation may be important in the biosynthesis of acridone alkaloids. 

Simple pyrroles do not react as 4n components in Diels-Alder cycloadditions exposure of pyrrole to benzyne, for example, leads only to 2-phenylpyrrole, in low yield. However A-substitution, particularly with an electron-withdrawing group, does allow such reactions to occur, for example adducts with arynes are obtained using l-trimethylsilylpyrrole. Whereas pyrrole itself reacts with dimethyl acetylenedicar-boxylate only by a-substimtion, even at 15 kbar, ° A-acetyl- and A-alkoxycarbonyl-pyrroles give cycload-ducts, addition being much accelerated by high pressure or by aluminium chloride catalysis. The most popular A-substituted pyrrole in this context has been A-Boc-pyrrole, with benzyne (from diazotization of anthranilic acid) for example, a 60% yield of the cycloadduct is obtained. ... 

The isolation of alkaloids bearing the 8-hydroxyquinoline moiety prompted postulation (17) of a biosynthetic pathway to 1 from the amino acid tryptophan, for which chemical analogies are known (22) (Scheme 2). It should be noted, however, that, in general, quinolines are biosynthesized from anthranilic acid (14). Biosynthesis of broussonetine (4) would involve condensation of two molecules of 1 with a molecule of acetyl-CoA followed by cyclization, as depicted in Scheme 3. 

Chlorination, acenaphthene, 69 acetophenone, 71 acetyl-p-toluidine, 72 anthranilic acid, 8 p-chlorotoluene in side chain, 74 8-ethylisothiuronium sulfate, 142 2-methylnaphthalene, 79 succinimide, 86 with NaClOs and HC1, 72 with sulfuryl chloride, 8 Chloromethylation, ethylbenzene, 146 p-xylene, 129 thiophene, 80... 

When groups such as hydroxyl or amino that are sensitive to oxidation are present as well as an alkyl group, then oxidation of the latter is seldom a smooth reaction. Amino groups can be acetylated, so that, for example, p-(acetylamino)benzoic acid is obtained from A-acetyl-p-toluidine by permanganate 404 anthranilic acid can be derived similarly from A-acetyl-o-toluidine. In such cases it is best to keep the reaction mixture neutral by adding magnesium sulfate. 

Acetylation of delectine yielded an jV,0-diacetyldelectine (160). Basic hydrolysis of delectine gave a parent amino alcohol (161) and anthranilic acid. Treatment of alkamine (161) with methyl iodide and sodium hydride afforded derivative 162, which was identical with 0,0-dimethyllycoc-tonine. Soviet chemists also reported the isolation of 0,O-dimethylly-coctonine (162) from the same plant. The complete assignments of all functional groups and their stereochemistry were made on the basis of comparisons of H NMR and mass spectral data with those of other lycoc-tonine-type alkaloids. 

Chlorosulphonation of 4 -chloro-o-acetotoluidine yields the eorresponding sulphonyl chloride derivative whieh on amination forms the sulphonamide derivative. Oxidation of the methyl moiety gives the respeetive anthranilamide derivative whieh on hydrolysis eliminates the acetyl group to yield the substituted anthranilic acid. Fusion of this amino acid with propionamide first gives rise to an intermediate by the loss of a mole of water and ultimately helps in the closure of the ring to generate the quinazoline ring system. Catalytic reduction of this finally produces the official compound. 

Fic. 1. Metabolism of tryptophan to serotonin (5-hydroxytryptamine) and niacin. Fyiidoxal phosphate (PLP) dependent reactions are indicated. Reactions not shown which may result in formation of products excreted in urine include the acetylation of liymuenine and 3-hydroxykynurenine, conjugation of anthranilic acid with glycine (to form o-aminohippuric acid) and with glucuronic acid, and the dehydroxylation of kynurenic acid and xanthurenic add to quinaldic add and 8-hydroxyquinaldic add, respectively. 

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid, and 1-deoxyxylulose 5-phosphate (Figure 2.1). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate, and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthranilic acid as aromatized CoA ester, anthraniloyl-CoA). Shikimic acid is a product of the glycol5dic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyr-uvate and erythrose 4-phosphate (Figure 2.1). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline, and acridine. 

Although several proposals and studies of the biosynthesis of vasicine (8) have been made, the complete biosynthetic route is not known with certainty, [carboxy Anthranilic acid is incorporated into vascicine in Adha-toda vasica with incorporation of the carboxyl label (Johne, 1986). It is established that anthranilic acid, probably as the A -acetyl derivative, also is incorporated. The acetyl portion accounts for the origin of C-3 and C-10. Aspartic acid may explain the origin of the remaining portion of the molecule (Johne, 1986) (Fig. 31.4). 

Acetic acid Acetic anhydride Acetone Acetyl chloride N-Acetylanthranilic acid Ammonium formate Ammonium hydroxide Anthranilic acid Benzaldehyde Benzene Benzyl chloride Benzyl cyanide... 

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