The Synthesis of α-Methyltryptophans and α-Alkyltryptamines

Heinzelman, R. V.; Anthony, William C.; Lyttle, Douglas A.; Szmuszkovicz, Jacob

doi:10.1021/jo01079a021

Cited by 55 publications

(20 citation statements)

References 2 publications

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“…Heinzelman et al, 1960;Hester et al, 1964;Snyder and Katz, 1947). Within about a decade of its first synthesis, α-ET was shown to interact with serotonin receptors of various isolated tissue preparations Khan, 1959a, 1959b;Gaddum et al, 1955;Vane, 1959) and to act as an inhibitor of monoamine oxidase (MAO) (Govier et al, 1953; Greig et al, 1953).…”

Section: Introductionmentioning

confidence: 99%

α-Ethyltryptamine (α-ET) as a discriminative stimulus in rats☆

Glennon

Bondareva

Young

2006

Pharmacology Biochemistry and Behavior

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Abstractα-Ethyltryptamine (etryptamine, α-ET) is a drug of abuse that first appeared on the clandestine market in the mid 1980s. Its pharmacological actions are poorly understood. In this investigation, it is reported for the first time that α-ET serves as a training drug in drug discrimination studies. Male Sprague-Dawley rats were trained to discriminate (30-min pretreatment time) 2.5 mg/kg of α-ET (ED 50 = 1.3 mg/kg) from saline vehicle using a standard two-lever operant paradigm and a VI-15s schedule of reinforcement for appetitive reward. Once established, the α-ET stimulus was shown to have an onset to action of 30 min and a duration of effect of at least 4 hours. In tests of stimulus generalization (substitution), the α-ET stimulus generalized to S(−)α-ET (ED 50 = 1.6 mg/kg) and R (+)α-ET (ED 50 = 1.3 mg/kg). Tests of stimulus generalization were also conducted with prototypical phenylisopropylamines: (+)amphetamine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), and N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA). The α-ET stimulus generalized to DOM (ED 50 = 0.4 mg/kg) and PMMA (ED 50 = 0.7 mg/kg), but only partially generalized (ca. 40% maximal drug-appropriate responding) to (+)amphetamine. The results suggest that α-ET produces a complex stimulus. Keywordsα-Ethyltryptamine; α-ET; (+)α-ET; (−)α-ET; DOM; PMMA; Amphetamine; Drug discrimination α-Ethyltryptamine, also known as etryptamine, α-ET, or AET, was first synthesized in 1947 as a potential synthetic precursor to the β-carbolines, and other syntheses have since been reported (e.g. Heinzelman et al., 1960;Hester et al., 1964;Snyder and Katz, 1947). Within about a decade of its first synthesis, α-ET was shown to interact with serotonin receptors of various isolated tissue preparations Khan, 1959a, 1959b;Gaddum et al., 1955;Vane, 1959) and to act as an inhibitor of monoamine oxidase (MAO) (Govier et al., 1953; Greig et al., 1953). The latter action, due to the growing interest at that time in the relationship between inhibition of MAO and depression, led to clinical trials of α-ET as an antidepressant. α-ET was soon thereafter (1961) introduced as an antidepressant ("Monase"); but, despite its apparent effectiveness (e.g. Robie, 1961), it was withdrawn from the market within a year of its introduction due to problems with agranulocytosis and other side effects. This led to the subsequent synthesis (Hester et al., 1964) and patenting (Anthony, 1970) of the individual optical isomers of α-ET-presumably in an attempt to divorce its therapeutic action from its † Presented at the College Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers th...

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Section: Introductionmentioning

confidence: 99%

α-Ethyltryptamine (α-ET) as a discriminative stimulus in rats☆

Glennon

Bondareva

Young

2006

Pharmacology Biochemistry and Behavior

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“…Reduction in nitrovinyl derivatives 5 with lithium aluminum hydride according to yields the corresponding 5‐aminomethyl‐2‐indolylpyrrolidines 6a,f , identified as hydrochlorides, as well as 6e identified as phenylthiocarbamoyl derivative because the amine hydrochloride one is very hygroscopic. Attempts at selective reduction in nitrovinyl group with sodium borohydride under various conditions were unsuccessful.…”

Section: Resultsmentioning

confidence: 99%

Condensations based on 5‐(indol‐3‐yl)‐pyrrolidin‐2‐thiones

Sadovoy

Kattsyna

Protopopova

et al. 2018

Heteroatom Chemistry

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New activated indolylpyrrolidones—their methylthiopyrrolinium salts—in the reactions with several CH‐acids were studied. 2‐Nitromethylene‐ and 2‐dicyanomethyleneindolylpyrrolidines were obtained from 5‐indolyl‐2‐methylthiopyrrolinium salts with good yields. The reduction in these nitro compounds yields the respective aminomethylpyrolidines. The rigid structure of the starting compounds has significant stereoelectronic requirements of nucleophilic agents.

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“…8 ) As a method of the synthesis, the Bucherer reaction using indoylacetone 9 ) and a condensation reaction of gramine with ethyl a-nitropropionate followed by reduction and saponification 10 ) have been reported. In this study, we synthesized a-methyltryptophan by the reaction of the isocyano compound with gramine methiodide for the introduction of indole moiety.…”

Section: A-m Ethyltryptophanmentioning

confidence: 99%

“…The resulting N-acetyl-amethyltryptophan (9) was identical with an authentic specimen. 9 ) In the reaction, the use of excess acetic anhydride gave the azlactone compound (10).…”

Section: A-m Ethyltryptophanmentioning

confidence: 99%