Amino-Indoles

2-Aminoindole exists mainly as the 3H-tautomer, presumably because of the energy advantage conveyed by amidine-type resonance. 3-Aminoindole is very unstable, and easily autoxidised. Both 2- and 3-acylamino-indoles are stable and can be obtained by catalytic reduction of nitro-precursors in the presence of anhydrides. 1-Amino-indoles can be prepared by direct amination of the indolyl anion.  

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In Figure 4.70, in the overall process, 5-nitroindole is reduced to amino-indole the chloride ion is present in the form of HG1 and the 5-nitroindole is protonated under these acid conditions. 

Corrections to condensation products have been made with 2,4-dimethylpyrroloquinoline arising from the reaction of 7-amino indoles with acetylacetone <1995SC1601, 1995CHE50> and not pyrrolobenzodiazepine as originally reported (Equation 162) <1957PCS354>. 

SYNS a -AMINO-3-INDOLEPROPRIONIC ACID tt-AMINO-INDOLE-3-PROPRIONIC ACID -a-AMINO-3-INDOLEPROPRIONIC ACID 2-Ai nNO-3-INDOL-3-YL-PROPRIONIC ACID EH 121 INDOLE-3-ALANINE l-P-3-INDOLYL LANLNE NCI-C01729 (-)-TRYPTOPHAN 1-TRYPTOPHAN (FCC) TRYPTOPHANE... 

AMINOHYPOXANTHINE see GUOOO a-AMINO-INDOLE-3-PROPRIONIC ACID see TNXOOO a -AMINO-3-INDOLEPROPRIONIC ACID see TNXOOO... 

In reducing conditions, alkylation of amino, indole, thiol, and thioether groups, and binding of saccharides to a.a. residues are possible ... 

To further extend fhe substitution pattern of fhese building blocks, benzarmelated N-amino-N-heterocycles were prepared Electrophilic amination of indole, 2-mefhylindole, or carbazole using hydroxylamine-O-sulfonic acid [25] yielded fhe corresponding N-amino-indole 17, -2-methyhndole 18, and -carbazole 19, respectively. However, attempting the same reaction with 2,7-dimethyhndole or dibenza-zepine (iminostilbene) failed, most likely due to steric hindrance. 

Reduction of 5- and 8-nitrocinnolines with zinc amalgam in aqueous acetic acid gives the corresponding 4- and 7-amino-indoles these conditions have previously been used to effect ring-contraction of 4-alkyl- and 4-aryl-cinnolines. Treatment of the perhydropyridazine (95) with hot concentrated sulphuric acid results in nearly quantitative rearrangement to the pyrazole (96). ... 

Quinazolin-2-one was obtained quantitatively by fusing 2-aminobenzaldehyde with urea (10 min at 150°C).76,91 Similarly, 2-amino-3-formylpyridine and urea (15 min at 160°C) gave an excellent yield of pyrido[2,3-d]pyrimidin-2-one (see 3).92 Finally, as an example from jt-excessive chemistry, 2-amino-indole-3-aldehyde was converted to its 2-benzyloxycarbonyl derivative, which benzylamine quantitatively converted to 3-benzyl-9f/-pyrimidino-[4,5- >]indol-2-one (87)93... 

Glu-P-2 Dipyrido[l, 2-a 3 , 2 -ai]imidazole, 2-amino-Indole glut trp lys leuc yes yes ... 

Lauria A, Diana P, Barraja P, Montalbano A, Dattolo G, Cirrincione G (2004) Docking of indolo- and pyrrolo-pyrimidines to DNA. New DNA-interactive polycycles from amino-indoles/pyrroles and BMMA. ARKIVOC 5(2) 263-271... 

Scheme 1 Synthesis of 1-amino indoles via Palladium-catalyzed intramolecular C-N bond formation...

The 5-endo-dig cyclization was observed for the Cu°-catalysed reaction of alkynyl substrates (207) with 0-benzoyl hydroxylamines (208), which gives rise to 3-aminobenzofurans (209a) and 3-amino indoles (209b), respectively. ... 

The yields of L-tryptophan produced by this method are impressive from 6 g of indole and 8 g of pyruvate in 100 ml of culture broth, 10 g of amino acid have been obtained. It was found important to add to the reaction mixture inosine, which form an insoluble complex with the synthesized L-tryptophan. When indole was replaced by 5-hydroxy-, 5-methyl- or 5-amino-indole, the corresponding 5-substituted L-trypto-phan was synthesized 449). 

Crystal stmctures of complexes of copper(II) with aromatic amine ligands and -amino acids " " and dipeptides" have been published. The stmctures of mixed ligand-copper complexes of L-tryptophan in combination with 1,10-phenanthroline and 2,2 -bipyridine and L-tyrosine in combination with 2,2 -bipyridine are shown in Figure 3.2. Note the subtle difference between the orientation of the indole ring in the two 1,10-phenanthroline complexes. The distance between the two... 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

The mode of action is by inhibiting 5-enolpymvyl-shikimate-3-phosphate synthase. Roundup shuts down the production of the aromatic amino acids phenylalanine, tyrosine, and tryptophane (30). Whereas all these amino acids are essential to the survival of the plant, tryptophane is especially important because it is the progenitor for indole-3-acetic acid, or auxin, which plays an important role in growth and development, and controls cell extension and organogenesis. 

The indole ring is incorporated into the stmcture of the amino acid tryptophan [6912-86-3] (6) and occurs in proteins and in a wide variety of plant and animal metaboUtes. Much of the interest in the chemistry of indole is the result of efforts to understand the biological activity of indole derivatives in order to develop pharmaceutical appHcations. 

Naturally Occurring Compounds. Many derivatives of iadole are found ia plants and animals where they are derived from the amino acid tryptophan. Several of these have important biological function or activity. Serotonin [50-67-9] (12) functions as a neurotransmitter and vasoconstrictor (35). Melatonin [73-31-4] (13) production is controlled daily by the circadian cycle and its physiological level iafluences, and seasonal rhythms ia humans and other species (36). Indole-3-acetic acid [87-51-4] (14) is a plant growth stimulant used ia several horticultural appHcations (37). 

Enzymatic Process. Chemically synthesized substrates can be converted to the corresponding amino acids by the catalytic action of an enzyme or the microbial cells as an enzyme source, t - Alanine production from L-aspartic acid, L-aspartic acid production from fumaric acid, L-cysteine production from DL-2-aminothiazoline-4-catboxyhc acid, D-phenylglycine (and D-/> -hydtoxyphenylglycine) production from DL-phenyUiydantoin (and DL-/)-hydroxyphenylhydantoin), and L-tryptophan production from indole and DL-serine have been in operation as commercial processes. Some of the other processes shown in Table 10 are at a technical level high enough to be useful for commercial production (24). Representative chemical reactions used ia the enzymatic process are shown ia Figure 6. 

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