Category Archives: Journal of Heterocyclic Chemistry

Synthesis of novel [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2‐a]thieno[2,3‐d] pyrimidines: Potent EGFR targeting anti‐breast cancer agents

Posted on 29 January 2024 by

Synthesis of fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d]pyrimidines using [3 + 2] reaction cycloaddition followed by C-C bond coupling in a PEG-400 medium. Anti-breast cancer activity against two breast cancer cell lines, MDA-MB-231 and MCF-7. The most promising compounds, 5g and 5i, demonstrated excellent anticancer activity against both cancer cell lines, with IC₅₀ values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.467 ± 0.063 and 0.412 ± 0.081 μM).

Abstract

In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d]pyrimidine derivatives using in a single [3 + 2] reaction cycloaddition reaction of 3-(3-iodoprop-2-yn-1-yl)thieno[2,3-d]pyrimidin-4(3H)-one (4) followed by C-C bond coupling with various aryl azides in a PEG-400 medium. All of the newly synthesized compounds were evaluated in vitro for EGFR kinase inhibitory action as well as anti-breast cancer activity against MDA-MB-231 and MCF-7 breast cancer cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 5g and 5i, demonstrated excellent anticancer activity against both cancer cell lines, with IC₅₀ values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.467 ± 0.063 and 0.412 ± 0.081 μM). The in silico studies of five potent compounds 5f, 5g, 5h, 5i, and 5k were also carried out to identify the interactions against the EGFR receptor and found that the energy calculations were covenant with the obtained IC₅₀ values.

Microwave‐assisted synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidines and pyrano[4,3‐b]pyrans catalyzed by L‐glutamine functionalized magnetic nanoparticles in water:ethanol mixture

Posted on 28 January 2024 by

This work presents a one-pot synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine and pyrano[4,3-b]pyran derivatives using the magnetic Fe₃O₄@SiO₂@L-glutamine nanoparticles as an organo-nanocatalyst. This protocol offers great efficiency, cost-effectiveness and environmental friendliness, with microwave irradiation and multicomponent reactions yielding excellent product yields, shorter reaction times, wider substrate scope, and formation of new compounds.

Abstract

In this work, we report an effective, one-pot syntheses of benzo[4,5]imidazo[1,2-a]pyrimidine and pyrano[4,3-b]pyran derivatives using L-glutamine functionalized nanoparticles (Fe₃O₄@SiO₂@L-glutamine NPs) under microwave irradiation. The organo-nanocatalyst underwent characterization through diverse techniques, including FT-IR, p-XRD, SEM, TEM, EDX, XPS, TGA, and VSM. Microwave irradiation and multicomponent reactions synergistically yield excellent product yields (≈80%–95%) in shorter reaction times (≈6–15 min) with a broader substrate scope. The organo-nanocatalyst displays notable catalytic efficacy, evidenced by high turnover numbers (TON) and turnover frequencies (TOF) across syntheses. This innovative protocol showcases exceptional efficiency, cost-effectiveness, and environmental friendliness, with advantages like minimal reaction conditions, easy catalytic recovery, recyclability, operational simplicity, and the use of eco-friendly solvents.

Chemoselective direct amidation of fatty acids with furfurylamine without coupling reagents in reversed micellar microenvironment

Posted on 26 January 2024 by nAyhan Yıldırım, nMehmet Suat Aksoyn

A convenient chemoselective and direct amidation method to access to fatty acids-based furfurylamides as versatile building blocks in Diels-Alder reactions.

Abstract

Furan heterocyclic compounds derived from renewable sources are popular versatile candidates for the production of multifunctional macromolecular materials. These compounds are also used as hydrophobilization monomers for reversible polyadducts or as versatile building blocks in Diels-Alder reactions. In the present study, an efficient approach to chemoselective acylation of furfurylamine with a series of non-preactivated monocarboxylic or dicarboxylic long-chain fatty acids and some of their functionalized derivatives has been achieved via catalytic direct amidation in reversed micellar medium. A convenient and environmentally friendly method has been developed for furfurylamides via a dehydrative coupling reaction. For this purpose, a new cationic Brønsted-type sulfonic acid catalyst containing a hexadecyl alkyl chain was synthesized and fully characterized. The present catalytic reaction produced the respective N-furfurylamides materials in good to excellent yields. This study also confirms that the direct amidation of carboxylic acids with selected amine compounds can be successfully catalyzed by Brønsted acids. Its simplicity and high atom economy are the main advantages of this method.

[3 + 2] Cycloaddition of nitrile oxides to dichloropropenes and 1,3‐dichlorobut‐2‐ene: A regioselectivity issue

Posted on 24 January 2024 by nAlexandra N. Shilova, nNina S. Shatokhina, nEvgeniy V. Kondrashovn

[3 + 2] Cycloaddition of nitrile oxides to chloroalkenes—common organochlorine wastes: experimental and DFT study.

Abstract

The reaction of nitrile oxides with 2,3-dichloroprop-1-ene, 1,3-dichloroprop-1-ene, and 1,3-dichlorobut-2-ene leads to 5-(chloromethyl)isoxazoles, 4-(chloromethyl)isoxazoles, or to mixtures of both regioisomers. The direction of cycloaddition and reactivity of substrate is determined by the steric hindrance at the terminal carbon atom of the alkene double bond. It has been found that the isomeric products of cycloaddition of nitrile oxides to 1,3-dichloropropene have significantly different dehydrochlorination capabilities. The experimental data on the regioselectivity of cycloaddition and the relative reactivity of substrates are in agreement with the results of quantum chemical calculations.

Synthesis and characterization of a highly fluorescent benzofuran dimer derived from estradiol

Posted on 23 January 2024 by

A steroid dimer bearing the 1,4-di(benzofuran-2-yl)benzene moiety obtained from estradiol showed an intense blue fluorescence band between 350 and 550 nm with a 18-fold-increased quantum yield compared with that of its synthetic precursor.

Abstract

Pd-catalyzed cyclization of a fluorescent dimer in which two cores of the potent estrogenic estradiol are bridged by the 1,4-diethynil benzene moiety led to a steroid dimer bearing the 1,4-di(benzofuran-2-yl)benzene. The obtained compound showed an intense blue fluorescence characterized by a broad emission band between 350 and 550 nm, with four maxima at 384, 403, 435, and 456 nm. The benzofuran dimer showed an 18-fold increased quantum yield compared with that of its synthetic precursor.

Application of the aza‐Wittig reaction for efficient synthesis of diversely substituted benzo[f]Chromeno[2,3‐d]pyrimidine and benzo[f]chromeno[2,3‐d][1,2,4]triazolopyrimidine derivatives

Posted on 23 January 2024 by

An effective iminophosphorane mediates the synthesis of a fused ring system with potent anticancer relevance via the Aza-Wittig reaction.

Abstract

An efficient synthesis of novel benzo[f]Chromeno[2,3-d]pyrimidine and unknown benzo[f]chromeno[2,3-d][1,2,4]triazolopyrimidine derivatives is described utilizing ethyl-2-amino-4-phenyl-4H-benzo[f]chromene-3-carboxylate as precursor via aza-Wittig reaction. The process proved to be simple, high-yielding, and efficient.