Indole-3-acetamide

Chemical Name 1 -(4-Chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1 H-indole-3-acetamide... 

Kostic el al. discovered that Pd11 complexes, when attached to tryptophan residues, can rapidly cleave peptides in acetone solutions to which a stoichiometric amount of water is added, for hydrolysis.436 The indole tautomer in which a hydrogen has moved from the nitrogen to C(3) is named indolenine. Its palladium(II) complexes that are coordinated via the nitrogen atom have been characterized by X-ray crystallography and spectroscopic methods.451 Binuclear dimeric complexes between palladium(II) and indole-3-acetate involve cyclopalladation.452 Bidentate coordination to palladium(II) through the N(l) and the C(2) atoms occurs in binuclear complexes.453 Reactions of palladium(II) complexes with indole-3-acetamide and its derivatives produced new complexes of unusual structure. Various NMR, UV, IR, and mass spectral analyses have revealed bidentate coordination via the indole carbon C(3) and the amide oxygen.437... 

The first report of enzyme catalyzed esterification of lAA was made by Kopcewicz et al. [117], who studied the synthesis of lAA esters by incubating radiolabeled lAA with a com endosperm enzyme preparation. Following incubation, ammonia was added to the incubation mixture and the amount of labeled indole-3-acetamide formed was used as a measure of the amount of lAA ester synthesized. Ester synthesis was found to be stimulated by ATP and CoASH, suggesting acyl group activation. Later studies by Michalczuk and Bandurski [118,119] used a more direct assay procedure, and indicated the following two step reaction mechanism involving sugar, not lAA, activation ... 

A careful study of indolic compounds produced by R. phaseoli showed that tryptophan could be converted into lAA, indole-3-ethanol, and indole-3-methanol, but indole-3-acetamide was not formed [189]. Bradyrhizobium, however, were shown to contain indole-3-acetamide as well as the indoleacetamide hydrolase activity, suggesting the presence of the tryptophan monooxygenase/indoleacetamide hydrolase pathway [190,191] in these organisms. 

Figure 5.42 Proposed tryptophan-dependent indole acetic acid biosynthesis pathways for Arabidopsis. Dashed arrows indicate that neither a gene nor enzyme activity has been identified in Arabidopsis. lAM, indole-3-acetamide IPA, indole-3-pyruvic acid lAAld, indole-3-acetaldehyde lAOx, indole-3-acetaldoxime 5-lAH-L-cys,...

Condensation of tryptamines (14,44) with indole-3-acetic acid (45) provides N-[2-(indol-3-yl)ethyl]indole-3-acetamides (46a, 81% 46b, 98%). Reduction of 46a with EtsSiH/TFA produces bis-2,3-dihydroindole derivative (47a, 90%), while the reduction with NaBHsCN gives rise to 47a (42%) and 48 (45%), a product reduced selectively at the tryptamine pyrrole part. 

Reduction of 46b with EtsSiH/TFA produces similarly N-methyl-bis-2,3-dihydroindole (47b, 85%). Employing the tungstate method, 47a,b and 48 are converted to N-[2-(l-hydroxyindol-3-yl)ethyl]-l-hydroxyindole-3-acet-amides (49a, 51% 49b, 39%) and N-[2-(l-hydroxyindol-3-yl)ethyl]indole-3-acetamide (50, 55%), respectively. Subsequent methylation of 49a,b and 50 affords 43a (91%), 43b (72%), and 51 (100%). 

The compound (49a) reacts with indole in 85% HCOOH to produce N- 2-[l-(indol-3-yl)indol-3-yl]ethyl indole-3-acetamide (138, 7%), N-[2-(indol-3-yl)ethyl]- (139, 3%), and N- 2-[l-(indol-3-yl)indol-3-yl]ethyl -l-(indol-3-yl)indole-3-acetamide (140, 39%). In a similar reaction, the compoimd (50) provides 138 (52%) and a dehydroxylated product (46a, 8%). 

When the enamine component is changed from 162 to l-(l-pyrroUdinyl)-cyclohexene (166), 52 affords 3-hydroxy-M5-methoxycarbonyl-2-(l-pyrroli-dinyl)-3ff-indole-3-ethanamine (167, 38%) as a sole isolable product. Similarly, l-hydroxy-Ar,AT-dimethylindole-3-acetamide (168a) provides 3-hydroxy-N,N-dimethyl-2-(l-pyrrolidinyl)-3ff-indole-3-acetamide (169, 21%) and N,N-dimethylindole-3-acetamide (168b, 26%). The structure of 167 is determined by X-ray single-crystal analysis. 

Bromo-16-hydroxy-8,17,19-tricosatriene-4,6-diynoic acid, in B-30087 6-Bromo-l//-indole-3-acetamide, in B-20046 6-Bromo-l//-indole-3-acetic acid, B-20046 6-Bromo-l//-indole-3-acetonitrile, in B-20046... 

I. The conversion of L-tryptophan to indole-3-acetamide by an enzyme system from Pseudomonas savastanoi. J. Biol. Chem. 241 3738-3744. 

Norharman is uncompetitive with L-tryptophan for rabbit intestinal IDO and linearly competitive with L-tryptophan for mouse liver TPO. Some p-carbolines in 11-13 selectively inhibit one enzyme or the other. Specific inhibition effect of p-carbolines is different between TPOs from mammalian and Pseudomonad sources. Similarly, indole-3-acetamide, -acetonitrile, and -acrylic acid exhibit a potent inhibition for mammalian TPO, while they moderately inhibit the Pseudomonad enzyme. These indole derivatives show no inhibition for IDO. From these results, the difference of the structures of the active sites among these enzymes from various sources is suggested. 

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