Synthesis of <i>S</i>(+) and <i>R</i>(‐)‐3‐(2‐aminopropyl)indole from ethyl‐<scp>D</scp>‐ and <scp>L</scp>‐tryptophanate

Repke, David B.; Ferguson, Wilfred J.

doi:10.1002/jhet.5570130417

Cited by 25 publications

(7 citation statements)

References 20 publications

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“…Furthermore, the stereoselectivity of AANAT could have preparative applications in the production of pharmacologically active ␣-methyltryptamine congeners (17).…”

mentioning

confidence: 99%

Indoleamine Analogs as Probes of the Substrate Selectivity and Catalytic Mechanism of Serotonin N-Acetyltransferase

Khalil

Angelis

Cole

1998

Journal of Biological Chemistry

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Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase (AANAT)) catalyzes the reaction of serotonin (or tryptamine) with acetyl-CoA to form N-acetylserotonin (or N-acetyltryptamine) and is responsible for the melatonin circadian rhythm in vertebrates. This study evaluates a series of indoleamine analogs as alternate substrates of AANAT. 3-Indolepropylamine and 3-indolebutylamine were chemically synthesized and found to be processed by AANAT, although 20-and 60-fold less efficiently compared with the natural substrate serotonin, respectively. Racemic ␣-methyltryptamine and N -methyltryptamine were also shown to be substrates for AANAT, again with reduced k cat and k cat /K m compared with serotonin. The enzyme did exhibit ϳ9:1 stereoselectivity for the R-enantiomer of ␣-methyltryptamine versus the S-enantiomer. By measuring the enzymatic rates versus increasing buffer microviscosity, it was demonstrated that diffusional release of product is most likely the principal rate-determining step for the enzymatic transformation of tryptamine (which has similar k cat and k cat /K m compared with serotonin). Analysis of k cat and k cat /K m versus pH for the poor substrate N -methyltryptamine showed that an ionizable group on the enzyme with pK a ϳ 7, required to be in its deprotonated form, may be important in catalysis. The ␣-methyltryptamine analog ␣-trifluoromethyltryptamine was not processed by the enzyme, but served as a modest competitive inhibitor. Taken together with the pH-rate analysis, these results favor a model in which the serotonin substrate binds to the enzyme as the positively charged ammonium salt, and nucleophilicity of the amine is important in enzyme-catalyzed acetyl transfer.

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“…Furthermore, the stereoselectivity of AANAT could have preparative applications in the production of pharmacologically active ␣-methyltryptamine congeners (17).…”

mentioning

confidence: 99%

Indoleamine Analogs as Probes of the Substrate Selectivity and Catalytic Mechanism of Serotonin N-Acetyltransferase

Khalil

Angelis

Cole

1998

Journal of Biological Chemistry

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“…An earlier report (18) as that used previously (18). In contrast to the corresponding indole analog, the N-benzyloxycarbonyl-O-ptoluenesulfonyl intermediate (IV) is a stable, crystalline solid.…”

Section: (+)-Isomers Of Amphetamine [Dextroamphetamine (V)]mentioning

confidence: 75%

Synthesis of Dextroamphetamine Sulfate and Methamphetamine Hydrochloride from D-Phenylalanine

Repke

Bates

Ferguson³

1978

Journal of Pharmaceutical Sciences

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“…Analysis was carried out using the indole C-2 proton and optical rotation data were also given. The levo-rotatory isomer was found to have the same configuration as levoamphetamine (R) [51].…”

Section: Repke Reported the First Asymmetric Synthesis Of S-(+)mentioning

confidence: 94%

“…and R-(−)-AMT from ethyl d-and l-tryptophanate [51]. A five-step synthesis starting from ethyl S-tryptophanate gave R-AMT.…”

Section: Repke Reported the First Asymmetric Synthesis Of S-(+)mentioning

confidence: 99%

An analytical perspective on favoured synthetic routes to the psychoactive tryptamines

Brandt¹,

Freeman

McGagh³

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

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Synthesis of S(+) and R(‐)‐3‐(2‐aminopropyl)indole from ethyl‐D‐ and L‐tryptophanate

Cited by 25 publications

References 20 publications

Indoleamine Analogs as Probes of the Substrate Selectivity and Catalytic Mechanism of Serotonin N-Acetyltransferase

Indoleamine Analogs as Probes of the Substrate Selectivity and Catalytic Mechanism of Serotonin N-Acetyltransferase

Synthesis of Dextroamphetamine Sulfate and Methamphetamine Hydrochloride from D-Phenylalanine

An analytical perspective on favoured synthetic routes to the psychoactive tryptamines

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