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一种用于可持续合成双杂环药物骨架的声化学和机械化学一锅多组分/点击偶联策略。

A Sonochemical and Mechanochemical One-Pot Multicomponent/Click Coupling Strategy for the Sustainable Synthesis of Bis-Heterocyclic Drug Scaffolds.

作者信息

Rentería-Gómez Manuel A, Calderón-Rangel David, Corona-Díaz Alejandro, Gámez-Montaño Rocío

机构信息

Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, C.P. 36050, Gto., México.

出版信息

Chempluschem. 2025 Jan;90(1):e202400455. doi: 10.1002/cplu.202400455. Epub 2024 Nov 8.

Abstract

Bis-heterocycles were synthesized via a consecutive one-pot process by a Groebke-Blackburn-Bienaymé reaction (GBB-3CR) followed by Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) assisted by alternative sustainable energies (ASE) such as ultrasonic and mechanical. These efficient and convergent strategies allowed the in situ generation of complex azides functionalized with imidazo[1,2-a]pyridines (IMPs), which was used as a synthetic platform. The target molecules contain two privileged scaffolds in medicinal chemistry: IMPs and the heterocyclic bioisostere of trans-amide bond, the 1,4-disubstituted 1H-1,2,3-triazoles (1,4-DS-1,2,3-Ts).

摘要

双杂环化合物是通过连续一锅法,经由格罗布克-布莱克本-比内梅反应(GBB-3CR),随后在超声和机械等替代可持续能源(ASE)辅助下进行铜催化的炔烃-叠氮环加成反应(CuAAC)合成的。这些高效且汇聚的策略使得能够原位生成用咪唑并[1,2-a]吡啶(IMPs)官能化的复杂叠氮化物,其被用作合成平台。目标分子在药物化学中包含两个优势骨架:IMPs以及反式酰胺键的杂环生物电子等排体,即1,4-二取代的1H-1,2,3-三唑(1,4-DS-1,2,3-Ts)。

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