Indole-3-carboxylic acid possible

Changing the functionality on the alicyclic ring from an amine to a carboxylic acid leads to a compound that shows antiallergic activity, acting possibly by means of inhibition of the release of allergic mediators. Thus, condensation of acylated indole with cyclohexanone carboxylic acid affords directly oxarbazole (29). ... 

For the retrosynthesis of indole (see Fig. 5.8), two routes (I/II) are proposed, as for pyrrole (see p 94). Route I suggests o-aminobenzyl ketone 1 or 6>-alkyl-A -acylaniline 2 as starting material on the basis of operations a - c. Their retroanalysis (d,e) in turn leads to 2-alkylaniline 5 and carboxylic acid derivative 6. Construction of the indole system should thus occur by N- or C-acylation of 5 (utilizing the o-nitrotoluene derivative 4) followed by cyclodehydration of 1/2. The alternative route n, based on retrosynthetic analysis g-i, leads to aniline via the a-(A -phenylamino)ketones 3 and to a-halo ketones 7 as possible precursors for the indole synthesis. 

A semi-systematic study of the hydrolysis of ethyl indole-2-carboxylate in aqueous media at high temperature indicated that decarboxylation of indole-2-carboxylic acid proceeded by an arenium ion mechanism and was inhibited by base. Because base facilitated hydrolysis of the ester, it was possible to obtain either the acid or indole from the ester merely by manipulating the number of equivalents of base present. 

Unfortunately, no lead sensors have been developed to date that meet all of these criteria. The system that has been used most extensively to quantitate lead levels in vivo is the fluorescent sensor Indo-1 (Fig. 24) (443 45). Although originally developed as a calcium dye (446) log iCfc[Ca(II)] = 6.6, Indo-1 (2-[4-[bis(carboxymethyl)amino]-3-[2-[2-[bis(carboxymethyl)amino]-5-methyl-phenoxy]ethoxy]phenyl]-lH-indole-6-carboxylic acid) binds lead quite tightly (log ffo[Pb(II)] = 10.5 and exhibits a very different fluorescence emission spectrum when bound to lead than when free in solution or bound to calcium (Fig. 24). As a result, Indo-1 can be used to determine whether lead is present in cells, even in the presence of excess calcium, provided that the fluorescence spectrum is deconvoluted to account for calcium interference and all of the possible equilibria are taken into consideration (443, 445). The main drawback of the Indo-1 detection system is that the dye is almost completely quenched when bound to lead (Fig. 24, spectrum b), making it difficult to quantitate the amount of free lead present. 

In some cases it is possible to obtain Diels-Alder adducts from vinylindole intermediates which are generated in situ. The yields in such reactions are usually not very high but the simplicity of operation is a compensating factor. For example, heating indole, a ketone and maleic acid together gives l,2,3,4-tetrahydrocarbazole-2-carboxylic acids in around 20% yield (Equation (143))... 

Substituted 7,12-dihydroindolo[3,2-c(][l]benzazepin-6(5/0ones 2a and 2b were first reported in 1958 by MacPhillamy et al. [33] as the last intermediate in an 11-step synthesis of 4-ethyl-5,6,7,12-tetrahydro-2-methylindolo[3,2-t/][l]benzazepine. In 1992, Kunick reported the preparation of six indolo[3,2-d][l]benzazepin-6(5/f)ones [34] in a three-step procedure. The crucial step was the decarboxylation reaction of 2,3-dihydro-5-hydroxy-2-oxo-l/7-benz[(t]azepin-4-carboxylic acid ethyl ester into 3,4-dihydro-lH-benz[ ]azepin-2,5-dione, which made possible the subsequent Fischer indole synthesis, with formation of the desired 7,12-dihydroindolo[3,2-fiT [l]benzazepin-6(5/f)ones. 

C-H alkenylation and decarboxylation (Scheme 4.48) [53], as in the reaction of benzoic acids described above (Schemes 4.28 and 4.29). Since the palladium-catalyzed Fujiwara-Moritani type direct alkenylation of indoles usually takes place at the C3-position, it enables alkenylation at a position complementary to that of the Fujiwara-Moritani reaction, being of unique synthetic utility. On the other hand, the reaction of thiophene-2-carboxylic acid leads to the formation of a mixture of C2- and C3-alkenylated products. Decarboxylation may take place too early to complete directed C-H alkenylation at the C3-position. In contrast, the exclusive C3-alkenylation on a thiophene ring is possible under rhodium catalysis (Scheme 4.49) [34b]. 

Cai and Ding designed a smart cascade process to construct indole-2-carboxylic acid esters 45 [42]. The possible reaction sequence is as follows (1) condensation of 2-haloaryl aldehydes (or ketones) 41 and ethyl isocyanoacetate to produce olefins 42 ... 

The major metal-binding amino acid side chains in proteins (Gurd and Wilcox, 1956 see Voet and Voet, 1990) (Table II) are carboxyl (aspartic acid and glutamic acid), imidazole (histidine), indole (tryptophan), thiol (cysteine), thioether (methionine), hydroxyl (serine, threonine, and tyrosine), and possibly amide groups (asparagine and glutamine, although... 

C-Metallation of indoles has, in nearly all cases, been conducted in the absence of the much more acidic iV-hydrogen i.e. the presence of an iV-substituent like methyl, or if required, a removable group phenyl-sulfonyl, lithium carboxylate and f-butoxycarbonyl have been used widely also recommended are dialkylaminomethyl, ° trimethylsilylethoxymethyl and methoxymethoxy (the Ai-substituent cannot be introduced into an indole - it requires a pre-formed 1-hydroxy-indole - but it is possible to reduce it off to leave an iV-hydrogen-indole). Each of these removable substituents assists lithiation by intramolecular chelation and in some cases by electron withdrawal, reinforcing the intrinsic tendency for metallation to proceed at the a-position. 

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