Indole alkylamines

Tyrischer Purpur, ein antiker Farbstoff, ein modernes Problem. Endevour 33, 11-17 (1974) 

Bender, D. A. Amino Acid Metabolism. Wiley, London 1975 

Alkaloids of neotropical poison frogs (Dendrobatidae). Prog. Chem. Org. Nat. Prod, 4i, 205-340 (1982) 

Gilchrist, D. G., Kosuge, T. Aromatic amino acid biosynthesis and its regulation. In The Biochemistry of Plants, Vol. 5, Amino Acids and Derivatives (B. J. Miflin, ed.), pp. 507-531, Academic Press, New York 1980 

Holzapfel, C. W. The biosynthesis of cyclopiazonic acid and related tetramic acids. In The Biosynthesis of Mycotoxins (P. S. Steyn, ed.), pp. 327-355. Academic Press, New York 1980 Schneider, E. A., Wightman, F. Metabolism of auxin in higher plants. Annu. Rev. Plant Physiol. 25, 487-513 (1974) 

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The hallucinogens generally fall into two chemical classes. The indole alkylamines include LSD, psilocybin, psilocin, dimethyltryptamine (DMT), and diethyltrypta-mine (DET), all of which are structurally similar to serotonin. The other chemical subclass of hallucinogens contains phenylethylamine derivatives such as mescaline, MDMA, MDA, and DOM (dimethoxymethyl amphetamine). A related stimulatory hallucinogen, PCP, is a piperidine analogue that produces unique effects. 

Berlin, J. and F. Sasse, 3-Carboline and indole alkylamines, in Cell Culture and Somatic Cell Genetics of Plants, Vol. 5 (I. K. Vasil, ed.), 357-369, Academic Press, Orlando, FL, 1988. 

Indole alkylamine derivatives are synthesized in microorganisms, plants and animals. 

Davis, V. E., Discussion remark to ref. 1867, Symposium Biological Role of Indole-alkylamine Derivatives, New York, 1967. 

The mutagenic properties of LSD-25 are now demonstrated and physicochemical studies by circular dichroism have shown direct interactions of LSD with calf-thymus DNA. Fluorescence studies also bring supporting evidence that indole-alkylamines can interact with DNA. Converging data are therefore at hand to support the provocative hypothesis of a direct competition of hallucinogens for tryptaminergic receptors located on DNA molecules in the nucleus or on RNAs located in the plasma membrane. 

Secondary and tertiary aminoalkylbenzotriazoles (108) react with pyrrole, indole, and their N-methyl analogues under mild conditions in the presence of a Lewis acid to afford selectively the corresponding secondary or tertiary aminoalkyl derivatives (Scheme 22) (92T4971). A,A-Bis(alk-oxymethyl)amines can also be used to give secondary alkylamines, which operate via reactive iminium salts formed by treatment with trimethylsilyl chloride (90TL4229). 

Erysophorine (13) was isolated from the water-soluble extract of the seeds of E. arborescens Roxb. (37). The molecular formula C32H38N304.CI was established by analysis. The mass spectrum of 13 gave no molecular ion but exhibited fragments consistent with a 1,6-diene Erythrina alkaloid and a carboxylated indole-3-alkylamine. Erysophorine appeared to be a combined alkaloid, and its UV spectrum was similar to that of an equimolar mixture... 

Indole-3-carboxylic acid amides 23a [21, 22] and esters 23b [23] can be obtained by irradiation in dichloromethane (DCM) of the 3-diazo-4-oxo-3,4-dihydroquino-line 21 in the presence of alkylamines, dialkylamines, arylamines or alcohols (ZH in Scheme 12.7), through a Wolff-type rearrangement involving a carbenoid species leading to the ketene-like intermediate 22 (Scheme 12.7). 

The amination of aryl halides and triflates catalyzed by palladium complexes is suitable for use in complex synthetic problems. Many substrates will produce high yields of mixed arylamines with one of the existing catalyst systems. Nevertheless, there are many combinations of substrates for which the amination chemistry may be substantially improved. For the most part, these reactions involve nitrogen centers, such as those in pyrroles, indoles, amides, imidazoles and other heterocyclic groups that are less basic than those in standard alkylamines. Although mild reaction conditions have been developed for many substrates, the harsh conditions used in many of the applications indicate that continued studies on developing mild condi-... 

A mixture of three products is obtained, in which the 7-methylated indole (62, R7 = Me) predominates (when methyl ethyl ketone is the ketone used), and predominates greatly when a substituent is present at position 4.64 The reaction mechanism is extremely complex, and the 7-methyl group is claimed to arise from the ethyl group of the ketimine. The synthesis is general, but gives a mixture of polyalkylated indoles in poor yield. Instead of a preformed alkylimine, a simple mixture of a dialkyl ketone and a primary alkylamine can be used. The N atom of the indole is provided by the alkylamine the N atom of the pyridinium salt is eliminated, along with the nitro group.65 67... 

Scheme 15.6 lron(0)-mediated oxidative cyclization of alkylamines to indoles. 

Sulfonamides are prepared from an amine and a sulfonyl chloride in the presence of pyridine or aqueous base. The sulfonamide is one of the most stable nitrogen protective groups. Most arylsulfonamides are stable to alkaline hydrolysis and to catalytic reduction they are cleaved by Na/NH3, Na/butanol, sodium naphthalenide, or sodium anthracenide, as well as by refluxing in acid (48% HBr/cat. phenol). Sulfonamides of less basic amines such as pyrroles and indoles are much easier to cleave than those of the more basic alkylamines. In fact, sulfonamides of the less basic amines (pyrroles, indoles, and imidazoles) can be cleaved by basic hydrolysis, which is almost impossible for the alkyl amines. Because of the inherent differences between the aromatic—NH group and simple aliphatic amines, the protection of these compounds (pyrroles, indoles, and imidazoles) will be described in a separate section. One appealing property of sulfonamides is that the derivatives are more crystalline than amides or carbamates. 

Enantioselective Friedel-Crafts reaction of indole with electron-rich alkenes by means of 21e furnished 1-indolyl-l-alkylamines, which are of pharmaceutical and biological importance, with excellent enantioselectivity (Equation 10.40) [84],... 

Incorporation of the alkylamine side-chain of trsrptamine into a tetrahydropyridine ring increases 5-HT,b receptor affinity hy more than 3 decades (Table 3). In contrast to the tryptamines, the 5-position of the indole nucleus of the... 

Oxidative cyclization of alkylamines tethered to tricarbonyl-cyclohexadiene complexes facilitates an easy route to synthesis of indole derivatives. The ring closure is brought about using a single-electron-transfer (SET) agent, such as ferricenium hexafluorophosphate. Yeh et al. reported the first intramolecular radical cyclization of jf-diene)Fe(GO)3 complexes, to afford racemic cyclic tertiary alcohols. 

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