Synthesis of Functionalized Triptamine Analogues with Dichloroethoxyphosphoryl and Ethoxycarbonyl Groups
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T COMMUNICATIONS In memory of M.M. Zobacheva and V.M. Berestovitskaya
Synthesis of Functionalized Triptamine Analogues with Dichloroethoxyphosphoryl and Ethoxycarbonyl Groups Z. M. Sarkisyana,* a St.
Petersburg State Pediatric Medical University, St. Petersburg, 194100 Russia * e-mail: [email protected] Received April 9, 2020; revised April 12, 2020; accepted April 16, 2020
Abstract—A rational method for the synthesis of functionalized tryptamine precursors by reduction of 1- and 2-substituted 3-nitroethylindoles on a nickel catalyst was proposed. Keywords: indolylaminoethylphosphonates, indolylaminopropanoates, tryptamine precursors
DOI: 10.1134/S107036322009025X Tryptamine and its analogs are of interest in terms of the possibility of synthesizing precursors of biologically active substances, including drugs [1]. Thus, the authors [2] have shown a successful decrease in nonspecific cytotoxicity and preservation of inhibition of the enzymatic activity of 2-[1-(3,4-dichlorobenzyl)-2-methyl5-(methylthio)-1H-indol-3-yl]ethanamine, as well as the ability of these compounds to bind to lipid II and have an antibacterial effect at low concentrations. On the other hand, melatonin derivatives, which can be considered as substituted tryptamine analogs, show antimutagenic activity [3]. Preclinical trials have also revealed the neuroprotective activity of new melatonin derivatives for the treatment of acrylamide-induced central neuropathy in rats [4]. In addition, some alkaloids contain a tryptamine fragment: lysergic acid, strychnine, clavine, etc. [5]. Tryptamine-based synthetic drugs are widely used. Among them are the anti-depressant indopan, the radioprotector mexamine, and the immunostimulant thymogen [1]. In this regard, the synthesis of tryptamine analogs with a broad spectrum of biological activity is of undoubted interest. An important factor in the preparation of such compounds is not only the simplicity of the process equipment, but also search for the most economical and rational synthesis routes. A convenient method in this regard is the hydrogenation of indolylnitroethylphosphonates
and -propanoates on a skeletal nickel catalyst at atmospheric pressure and room temperature in methanol (Scheme 1). The starting indolylnitroethylphosphonates 1, 2 and indolylnitropropanoates 3–5 were obtained by the procedures described in [6–8]. The target compounds 6–10 were isolated using column chromatography in 49–81% yield. Structure and composition of the obtained compounds were confirmed by IR, NMR spectroscopy and elemental analysis data. In summary, a simple and convenient method was proposed for the synthesis of tryptamine analogues with phosphonate and carboxylate functions, which may be of interest as substances with potential biological activity. Bis(2-chloroethyl) 2-amino-1-(indol-3-yl)ethylphosphonate (6). Hydrogen was passed through a solution of 0.79 g (0.002 mol) of bis(2-chloroethyl)-1-(indol-3yl)-2-nitroethylphosphonate in 17 mL of methanol in the presence of a nickel catalyst (1 g of nickel in 15 mL of abs
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