Enzymatic synthesis of tryptamine and its halogen derivatives selectively labeled with hydrogen isotopes

Abstract

Nine isotopomers of tryptamine and its halogen derivatives, labeled with deuterium, tritium in side chain, i.e., [(1R)-2H]-, [(1R)-3H]-, 5-F-[(1R)-2H]-, 5-F-[(1R)-3H]-, 5-Br-[(1R)-2H]-, double labeled [(1R)-2H/3H]-, 5-F-[(1R)-2H/3H]-, and ring labeled [4-2H]-, and [5-2H]-tryptamine, were obtained by enzymatic decarboxylation of l-Trp and its appropriate derivatives in deuteriated or tritiated media, respectively. Intermediates: [5′-2H]-l-Trp used for further decarboxylation was synthesized by enzymatic coupling of [5-2H]-indole with S-methyl-l-cysteine, and [4′-2H]-l-Trp was obtained by isotope exchange 1H/2H of the authentic l-Trp dissolved in heavy water induced by UV-irradiation. Doubly labeled [(1R)-2H/3H]- and 5-F-[(1R)-2H/3H]-tryptamine were obtain by decarboxylation of l-Trp or [5′-F]-l-Trp carried out in 2H3HO incubation medium.

Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention

“…Halogenated tryptamine derivatives have been suggested as potential radiopharmaceuticals for monitoring abnormal brain states occurring in Parkinson’s and Alzheimer’s diseases and schizophrenia [50, 51] and tryptamine Schiff bases were proposed as antimicrobial agents [52] (Table 3). Tryptamine has also been targeted in plant biochemistry and biology, both as the precursor of the plant auxin IAA and as a proto-alkaloid in tobacco plant biology and of hallucinogenic derivatives.…”

Biomedical Significance of Tryptamine: A Review

“…The studies shows that enzymatic decarboxylation of amino acids leads to alkaloids such as L-ADDC enzyme found in serum of various animals and humans is an effective catalyst for tryptamine production as well as pyridoxal phosphate (PLP) distributed in mammalian tissues responsible for the production of serotinine and melatonin [21]. The regional distribution in both striatum and hypothalamus of 5-hydroxytryptamine a well-known neurotransmitter helps in regulation of alcoholism in humans as well as mood, sleep and anxiety in mammals [22].…”

Enzymatic oxidation of substituted tryptamines catalysed by monoamine oxidase

“…2, by enzymatic decarboxylation of 5-F-L-Trp in fully deuteriated Tris·DCl buffer (pD 5.5). The reaction was carried out and product was separated and purifi ed as described earlier [19]. …”