Efficient synthesis of imino-1,3-thiazinan-4-one promoted by acetonitrile electrogenerated base and computational studie
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Efficient synthesis of imino‑1,3‑thiazinan‑4‑one promoted by acetonitrile electrogenerated base and computational studies with CB1 and 11 βHSD1 molecules Najoua Sbei, et al. [full author details at the end of the article] Received: 3 August 2020 / Accepted: 17 September 2020 © Springer Nature B.V. 2020
Abstract A novel and convenient strategy is described for the conversion of N, N′disubstituted thioureas and acryloyl chloride into the highly biologically valuable imino-1,3-thiazinan-4-one derivatives. The synthesis proceeds through a process with good yield promoted by an electrogenerated base obtained with high current efficiency. In addition to this, based on structure–activity relationship studies, we have found suitable targets like G-protein coupled (CB1) cannabinoid receptor and human 11 beta-hydroxysteroid dehydrogenase type 1 (11 βHSD1) for this synthesized molecule. The molecular docking studies were carried for our compound with CB1 and 11 βHSD1 to understand the binding interaction mechanism, and molecular dynamics simulations were performed to understand the stability of small molecule in CB1 and 11 βHSD1 microenvironments. Also, to understand the intermolecular stability density functional theory calculations were carried for free compound and compound in complex with CB1 and 11 βHSD1. Graphic abstract
Keywords N, N′-disubstituted thioureas · Electrogenerated base · Imino-1,3thiazinan-4-one · Organic acryloyl chloride · Molecular docking · Molecular dynamics · DFT Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116 4-020-04276-8) contains supplementary material, which is available to authorized users.
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Fig. 1 Model of biologically active six-membered derivatives
Introduction Organic electrochemistry presents a green process for the synthesis of the heterocycle compounds. In the last two decades, numerous papers reported the generation and the use of direct oxidation of substrates such as amine derivatives [1] for the synthesis of N-heterocycles [2], the oxidation of sulfur substrates for the synthesis of S-heterocycles [3], or the direct electrolysis of benzoic acids derivatives for the electrochemical formation of O-heterocycles [4–6]. On the other hand, it well established the efficacy and the use of strong basic species generated through electrolysis of organic aprotic solvents such as dimethyl sulfoxide, dimethylformamide, acetonitrile, and their application in organic synthesis on the synthesis of N-heterocycles like quinazolinones derivatives [7], imino1,3-thiazolines [8], imidazolidinones [9], imidazole carboxylates [10], oxothiazoldines [11], and triazinane derivatives [12]. Recently, it was demonstrated that the cyanomethyl anion could provide a cyanide anion to proceed cyanation of organic substrates [13]. Nowadays, the search for compounds having a medicinal application is of main interest, mostly the six-membered ring compounds which showed an interesting pharmaceutic activity [14, 15], such
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