Wang Manman, Ye Wenjun, Sun Nannan, Yu Wenquan, Chang Junbiao
Green Catalysis Center and College of Chemistry, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
J Org Chem. 2023 Jan 20;88(2):1061-1074. doi: 10.1021/acs.joc.2c02509. Epub 2023 Jan 11.
An iodine-mediated intramolecular sp C-H amination reaction producing quinazolinone-fused polycyclic skeletons from 2-aminobenzamide precursors is reported. This reaction does not use transition metals, has a broad substrate scope, and can be used on a gram scale. Under the optimal reaction conditions, a variety of quinazolinone-fused tetrahydroisoquinolines and derivatives of Rutaecarpine were synthesized from readily accessible compounds. The reaction proceeds well with crude 2-aminobenzamide derivatives, allowing for the synthesis of the products from simple 2-aminobenzoic acids and tetrahydroisoquinolines without purification of the 2-aminobenzamide intermediates. Preliminary biological experiments have identified Cereblon (CRBN) inhibitory activity and relevant anti-myeloma medicinal properties in some of these polycyclic products.
报道了一种碘介导的分子内sp C-H胺化反应，该反应可从2-氨基苯甲酰胺前体生成喹唑啉酮稠合的多环骨架。此反应不使用过渡金属，底物范围广泛，且可用于克级规模。在最佳反应条件下，由易于获得的化合物合成了多种喹唑啉酮稠合的四氢异喹啉和吴茱萸次碱衍生物。该反应对粗制的2-氨基苯甲酰胺衍生物也能很好地进行，无需纯化2-氨基苯甲酰胺中间体，即可从简单的2-氨基苯甲酸和四氢异喹啉合成产物。初步生物学实验已在其中一些多环产物中鉴定出对 Cereblon (CRBN) 的抑制活性及相关的抗骨髓瘤药用特性。
