Of indole-3-propionic acid

Substituents at the amide nitrogen with strong electron-attracting groups influence the amide imidole tautomerism and prevent intramolecular participation and elimination. Thus, the p-nitroanilide of indole-3-propionic acid was not cleaved by iV-bromosuccinimide (Table VI). 

V-Bromoacetamide, which reacts much more slowly than iV-bromosuc-cinimide with indoles, cleaves peptides of indole-3-propionic acid and acyl-tryptophans in yields comparable with those obtained with V-bromosuc-cinimide (Table VI). Slight variations fall within the limit of error ( 5%) of the analytical method. 

The half-life of a 0.0001 M solution of indole-3-propionic acid in the presence of 3 moles of iV-bromoacetamide (NBA) is about 7 min at room temperature, while V-bromosuccinimide reacts instantaneously. This is at variance with the general statement in the literature (Barakat et al., 1955) that V-bromoacetamide is considerably more reactive than V-bromosuc-cinimide (cf. Schmidt et al., 1926 Buckles et al., 1957). 

Analysis of endogenous IAA. The extracts of cells with methanol were subjected to solvent fractionation using methylene chloride to give methylene chloride soluble acidic fractions. The fractions were purified by HPLC on an ODS column and finally by HPLC on a Nucleosil 5N(CH3>2 column with a fluorescent detector. Quantification was made by using an internal standard of indole-3-propionic acid which was added before purification. The results are shown in Figure 7. 

Fig. 17. GLC of a mixture of indole derivatives (1 /jg of each derivative injected). For conditions see text. IAN = indole-3-acetonitrile lAA-ME = methyl ester of in-dole-3-acetic acid lAA-EE = ethylindole 3-acetate ICA-ME = methyl ester of in-dole-3-carboxylio acid IPA-ME = methyl ester of indole-3-propionic acid IBA-ME = methyl ester of indole-3-butyrio acid 6-OH-IAA-ME = 5-hydroxyindole-3-acetic acid (methyl ester). Reproduced from Brook et al. (B22) with permission.

Treatment of indole-3-propionic acid with 3 equiv. of NBS in aqueous media leads to the cyclic product 5-bromolactone (96) (295). Similar spirolactone formation has been found also with indole 3-propionyl... 

Fig. 8. Selected examples of aromatic donor molecules that form complexes with HRP C. The apparent dissociation constant for complex formation with the resting state plant enzyme is given (original references should be consulted for details of solution conditions and error estimations). (1) 2-Naphthohydroxamic acid (228) (2) benzhydroxamic acid (228) (3) 2-hydroxybenzhydroxamic acid (salicyUiydroxamic acid) (228) (4) benzhy-drazide (228) (5) cyclohexylhydroxamic acid (228) (6) 4-methylphenol (p-cresol) (192) (7) 2-methoxyphenol(guaiacol) (192) (8) indole-3-propionic acid(24i) (9)p-coumaric acid (238) (10) aniline (243).

Structural information on aromatic donor molecule binding was obtained initially by using H NMR relaxation measurements to give distances from the heme iron atom to protons of the bound molecule. For example, indole-3-propionic acid, a structural homologue of the plant hormone indole-3-acetic acid, was found to bind approximately 9-10 A from the heme iron atom and at a particular angle to the heme plane (234). The disadvantage of this method is that the orientation with respect to the polypeptide chain cannot be defined. Other donor molecules examined include 4-methylphenol (p-cresol) (235), 3-hydroxyphenol (resorcinol), 2-methoxy-4-methylphenol and benzhydroxamic acid (236), methyl 2-pyridyl sulfide and methylp-tolyl sulfide (237), and L-tyrosine and D-tyrosine (238). Distance constraints of between 8.4 and 12.0 A have been reported (235-238). Aromatic donor proton to heme iron distances of 6 A reported earlier for aminotriazole and 3-hydroxyphenol (resorcinol) are too short because of an inappropriate estimate of the molecular correlation time (239), a parameter required for the calculations. Distance information for a series of aromatic phenols and amines bound to Mn(III)-substituted HRP C has been published (240). 

Indole-3-Acetic Acid. Dissolve 21.6 g of phenylhydrazine in 300 ml 0.3 N sulfuric acid. To this solution add 9.8 g of coned sulfuric acid. With stirring and heating to 100°, add dropwise 11.6 g of methyl-beta-formyl-propionate in 300 ml of 0.3 N sulfuric acid. Continue the heating and gentle stirring for 6 hours to get about 14 g of indole-3-acetic acid. This is from CA, 72, 66815 (1970). 

In addition to tryptophan, /3-methylindole, indole-3-acetic acid and indole-3-propionic acid were tested under identical conditions and molar concentrations. The intensities of the color developed with 30 percent perchloric acid alone were in the order tryptophan < indole-3-acetic acid < indole-3-propionic acid < /3-methylindole. The first three of these indole derivatives produced red condensates with desoxyribose in perchloric acid, that due to indole-3-acetic acid being markedly less than that arising from the other two. 

Competitive inhibition of the carboxypeptidase from A. saitoi by small substrates was found with hydrocinnamic acid, indole-3-propionic acid, and 4-phenylbutyric acid [80], The K for hydrocinnamic acid inhibition was 4 x 10 4 M. Diisopropylfluorophosphate (DFP) and tosyl-L-phenylalanylchloromethane (TPCK) were also powerful inhibitors of the carboxypeptidase from A. oryzae (80). />-Chloromercuribenzoate (PCMB) and iodoacetic acid were also powerful inhibitors of the carboxypeptidase from A. saitoi, while the inhibitors of DFP, TPCK, PCMB, and iodoacetic acid on the carboxypeptidase from A. saitoi were less than that of A. oryzae [80], As the carboxypeptidase activity of A. saitoi has no effect when used with ethylenediaminetetraacetate (EDTA) and o-phenanthroline, the enzyme is a different type of carboxypeptidase from those of the pancreatic sources, carboxypeptidase A and carboxypeptidase B [80],... 

Fig. 3. Selected conformations of indole a-propionic acid viewed from the top of the molecule. While conformations (a) to (c) have been suggested as being conformations giving rise to activity, only conformation (d) is permissible for all the active S-and R-a-propionic acids.

In screening indole compounds for neuroprotection against amyloid P-protein, potent neuropro-tective properties were uncovered for an endogenous related species, indole-3-propionic acid, the capacity of which to scavenge hydroxyl radicals exceeded that of melatonin (Chyan et al. 1999). 

Mossbauer spectra of mixed Fe(lll) nitrate and indole-3-alkanoic acid aqueous solutions (molar ratios 1 3 initial Fe(lll) concentration 0.01 M) filtered and rapidly frozen (at T = 80 K) 15 min (a-d) and 2 days (e-h) after mixing the reagents (final pH 3). Acids used (a), (e)—ICA (b), (f)—lAA (c), (g)—indole-3-propionic acid (IPA) (d), (h)— indole-3-butyric acid (IBA). The position of the components related to Fe(ll) (shaded areas) is shown in the upper plots by square brackets. (Adapted from Refs. 46, 47.)... 

By introduction of methyl groups into the side-chain of lAA the interesting a-indole-3-propionic acid (Vc) and indole-3-isobutyric acid (Vd) are obtained. The assay of Vc in different tests led to a discussion on the importance of optical activity for growth-substance activity, which will be dealt within Section ii. 

It is perhaps because of the fact that an asymmetric structure, leading to optical activity, apparently is not a prerequisite for growth substance activity, that the early work of Kogl and Verkaaik ona-indole-3-propionic acid... 

Such a reversible blocking of the 2-position by sulfenylation was of particular interest in the synthesis of bromo-derivatives of indolyl-3-propionic acid. Specific bromination or nitration of the benzene ring of an indole is normally difficult to achieve, since the pyrrole ring also will react with electrophilic reagents. As an example, 5-bromoindole-3-propionic acid has been prepared using this reversible protection, that is by bromination of the 2-sulfenylated compound and removal of the arylthio group by the two consecutive reactions with NBS and NaBKi (727). 

N-Acetyl-tryptophan and indole-3-propionic acid have been labelled with deuterium and tritium by Spande and Fontana 371), who employed the corresponding 2-sulfenyl derivatives. The spirolactones (176) obtained from (175) by treatment with N-bromosuccinimide were reduced with NaBD4 or NaBTa in good yields back to the corresponding indole compounds specifically labelled with deuterium or tritium at the 2-position. The method seems to offer a new general procedure which permits introduction of label specifically at the 2-position of indoles bearing a propionic acid side chain at the 3-position. 

May and Moody (52) have reported a full account of their Diels-Alder cycloaddition route to ellipticine (1) and isoellipticine (27) (Scheme 10). Conversion of indole (50) to 3-indole-2-propionic acid (56) with lactic acid was followed by a Plieninger cyclization to the pyranoindole 57. Reaction of 57 with 3,4-pyridyne (59), as generated from triazene 58, afforded equal amounts of ellipticine (1) and isoellipticine (27). Although the overall yield of 1 from indole is only 3%, the sequence involves only three steps. 

Purification of 2-(4 -[ I]iodo-biphenyl-4-sulfonylamino)-3-(l//-indol-3-yl)-propionic acid and 2-(4 -[ I]iodo-biphenyl-4-sulfonylamino)-3-(lff-indol-3-yl)-propionamide... 

The cyclocondensation of 3-aminopyrido[3,4-h]indole (1090) and EMME in boiling acetic acid and propionic acid for 8 hr or 4 hr gave pyrimido[2, 1 6,1 ]pyrido[3,4-b]indolecarboxylate(1091) in52%and65% yields, respectively [87MIP4, 87MIP5 881JC(B)484]. 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The sulfones 367 (R = H and Me) obtained from 3-(indol-3-yl)propionate esters with the anion of dimethyl sulfoxide were cyclized, losing methylthiol, via 368 in the presence of p-toluenesulfonic acid in hot acetonitrile, ... 

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