芳基炔丙基醚的环化反应合成色烯类化合物及其衍生物

Cyclization of Aryl Propargyl Ethers for the Synthesis of Chromenes and Their Derivatives

摘要: 色烯类化合物具有广泛的生物活性。本文采用全合成的方法从简单化合物出发合成了一系列氰化改性2H-色烯类化合物并探究了其体外抗菌活性。以Williamson醚合成法高效制备了一系列炔醚类化合物，随后通过Sonogashira偶联反应将炔醚化合物与多种碘代芳烃及杂环化合物进行偶联，高收率的合成了一系列结构多样的炔醚–偶联产物。继而以N-碘代丁二酰亚胺(NIS)为亲电试剂，实现了炔醚–偶联产物的分子内亲电环化反应构建2H-色烯骨架并开展了2H-色烯类化合物的官能团改性研究，成功将氰基引入2H-色烯骨架，获得一系列氰基改性产物。最后，对12种氰基改性2H-色烯化合物进行了体外抑菌活性评价。结果表明，部分化合物对大肠杆菌具有一定抑制效果，而超过半数化合物对金黄色葡萄球菌表现出显著抗菌活性，测试体系中有一半形成了明显抑菌圈，显示出良好的应用潜力。

Abstract: Chromene compounds exhibit a broad spectrum of biological activities. This study employed a total synthesis approach to prepare a series of cyano-modified 2H-chromene derivatives from simple starting compounds and investigated their in vitro antibacterial activity. A series of alkynyl ethers were efficiently synthesized via Williamson ether synthesis. Subsequently, these alkynyl ethers were coupled with various iodoarenes and heterocyclic compounds through Sonogashira coupling reactions, yielding a diverse array of alkynyl ether-coupled products in high yields. Following this, an intramolecular electrophilic cyclization of the coupled products was achieved using N-iodosuccinimide (NIS) as the electrophile, successfully constructing the 2H-chromene scaffold. Further functional group modification studies on the 2H-chromene derivatives were conducted, leading to the successful introduction of cyano groups into the framework, which afforded a series of cyano-modified products. Finally, the in vitro antibacterial activities of 12 cyano-modified 2H-chromene compounds were evaluated. The results indicated that some compounds exhibited certain inhibitory effects against Escherichia coli, while over half demonstrated significant antibacterial activity against Staphylococcus aureus. Notably, half of the compounds in the test system formed distinct inhibition zones, revealing promising application potential.