Methoxy-indole

Dissolve the OH-indole in ethanol (0.14 M in 50 ml) and add 28 ml dimethylsulfate and 1.2 g Na hydrosulfite. Add slowly with stirring and cooling (under N2 if possible) 12 g NaOH dissolved in 26 ml water (keep temperature at 20-25°). Heat to 70° for one-half hour, cool and dilute with an equal volume water. Extract the yellow oil into ether-benzene and dry, filter, and evaporate in vacuum to get the methoxy-indole. 

Illustrated for 5,6,7-trimethoxyindole (for the trimethyl-indole see JOC 25,1542(1960)). 2-methoxy-beta-nitro-styrene, if nitrated at the 6 position and used in place of (I), should give 4-methoxy-indole. 

TRYPTAMINE, N-ACETYL-5-METHOXY INDOLE, 3-(2-ACETAMIDOETHYL)-5-METHOXY SEROTONIN, N-ACETYL-O-METHYL ACETAMIDE, N-[2-(5-METHOXYINDOL-3-YL)ETHYL] N-ACETYL-5-METHOXYTRYPTAMINE 3-(2-ACETAMIDOETHYL)-5-METHOXYINDOLE N-ACETYL-O-METHYLSEROTONIN N-[2-(5-METHOXYINDOL-3-YL)ETHYL]ACETAMIDE REGULIN... 

On the other hand toluene (4) and 5-methoxy-indole (5) would not be considered very similar from a conventional point of view, yet their hemolytic activity is the same (logl/C = 1.93, where C is the minimal molar concentration which causes 100% hemolysis in rabbit erythrocytes l)). Obviously, topological similarity or dissimilarily is not always a factor which is relevant for biological activity. In the present example the relevant feature is a physicochemical property of the compounds, i.e. lipophilicity as expressed by the octanol/water partition coefficient... 

Many early claims of having prepared simple 1-hydroxyindoles have proved to be unfounded, although the unusually stable l-hydroxy-2-phenylindole was obtained in 1895.1-Hydroxyindole itself polymerizes on attempted isolation, while O-acylation, O-alkylation, or the presence of substituents greatly stabilizes the molecule. One 1-hydroxyindole antibiotic has been identified and is the only 1-hydroxyindole derivative isolated from natural sources so far. In contrast, a substantial number of 1-methoxyindoles occurs in various plants, and some of these may inhibit tumor formation in mammals. The biochemistry of these compounds, which include 1-methoxy-indoles, -indolines and -2-oxindoles, has not been widely investigated and could be a very fruitful area for new research which might well lead to novel medicinal agents and other useful compounds. 

The indomethacin hydrolysis product 2-methyl-5-methoxy indole acetic acid fluoresces at 385 nm after excitation at 300 nm in 0.1N NaOH,(41) and at 387 nm after excitation at 312 nm in pH 11.6 buffer(42). The latter procedure claimed a threefold increase in detectability. Neither method distinguishes indomethacin from salicylates. Clinical studies employing subjects administered aspirin must use a separation prior to fluorescence analysis. Without adequate separation the indole metabolites as well as salicylate, produce a positive assay bias. 

Preparation of l-carboxymethyl-2-methyl-3-p-chlorobenzoyl-6-methoxy-indole... 

MeO-DIPT TRYPTAMINE, N,N-DIISOPROPYL-5-METHOXY INDOLE, 3-[2-(DIISOPROPYLAMINO)ETHYL]-5-METHOXY N,N-DIISOPROPYL-5-METHOXYTRYPT AMINE 3-[2-(DIISOPROPYL-AMINO)ETHYL]-5-METHOXYINDOLE... 

Methoxy indole-containing combretastatin derivatives, (I), and prodrugs, (II), prepared by Pinney (2) were found effective as antimitotic and antitubulin polymerization agents and used in the selective destruction of tumor cell vasculature. 

The results of carrying out both method I and II upon a mixture of 5-methoxy-indole (MOI) and 2-amino pyridine (AMP) in water are shown below ... 

Analog reagiert 5-Methoxy-indol mit Lithium/Ammoniak/Methanol zu 5-M ethoxy-4,7-dihydro-indol9 (80-82% d.Th. F 65-68°) und 5-Methoxy-3-(2-trimethyl-ammoniono-athyl)-indol-jodid zu 5-Methoxy-3-(2-trimetliylammoniono-dthyl)-4,7-dihydro-indol-jodid (4,7-Dihydro-tryptamin-methojodid)10 (43% d.Th. F 181-183°) ... 

Oxidation of rauvanine, a 9-methoxy indole alkaloid of known 19 8-methyl normal conhguration, with <-butyl hypochlorite gives rise to two oxindoles designated as rauvanine oxindole A (64 mp 234-236°) and B (65 mp 210-212°) which must belong to the normal series (57). The relatively shielded position of the C-19 proton of both oxindoles, when compared with the mitraphyllines, is in agreement with their formulation as 19j8-methyl normal oxindoles. 

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