A practically convenient and streamlined protocol for the trans-diastereoselective introduction of an aryl substituent at position 4 of the 1,4-dihydroisoquinol-3-one (1,4-DHIQ) scaffold is presented. The protocol involves direct Regitz diazo transfer onto readily available 3(2H)-isoquinolones followed by TfOH-promoted hydroarylation by an arene molecule. Screening of the novel 1,2,4-trisubstituted 1,4-DHIQs against cancer cell lines confirmed high cytotoxicity of selected analogs, which validates this new chemotype for further investigations as anticancer cytotoxic agents.
本文介绍了一种实用、简化的方案,用于在1,4-二氢
异喹啉-3-酮(1,4-DHIQ)支架的4位引入芳基取代基的
trans-对映选择性引入。该方案涉及直接Regitz重氮转移到易得的3(2
H)-
异喹啉酮上,然后通过TfOH促进的芳基烷基化反应与
芳烃分子反应。对新型的1,2,4-三取代的1,4-DHIQs进行癌
细胞系的筛选,确认了所选类似物的高细胞毒性,证实了这种新的
化学类别可以作为抗癌细胞毒剂的进一步研究对象。