Shoji Taku, Takeuchi Mutsumi, Uda Mayumi, Ariga Yukino, Yamazaki Akari, Sekiguchi Ryuta, Ito Shunji
Department of Chemical Biology and Applied Chemistry, College of Engineering, Nihon University, Koriyama 963-8642, Japan.
Graduate School of Science and Technology, Shinshu University, Matsumoto 390-8621, Japan.
Molecules. 2023 Jul 31;28(15):5785. doi: 10.3390/molecules28155785.
Quinolone and quinoline derivatives are frequently found as substructures in pharmaceutically active compounds. In this paper, we describe a procedure for the synthesis of azuleno[2,1-]quinolones and quinolines from 2-arylaminoazulene derivatives, which are readily prepared via the aromatic nucleophilic substitution reaction of a 2-chloroazulene derivative with several arylamines. The synthesis of azuleno[2,1-]quinolones was established by the Brønsted acid-catalyzed intramolecular cyclization of 2-arylaminoazulene derivatives bearing two ester groups at the five-membered ring. The halogenative aromatization of azuleno[2,1-]quinolones with POCl yielded azuleno[2,1-]quinolines with a chlorine substituent at the pyridine moiety. The aromatic nucleophilic substitution reaction of azuleno[2,1-]quinolines bearing chlorine substituent with secondary amines was also investigated to afford the aminoquinoline derivatives. These synthetic methodologies reported in this paper should be valuable in the development of new pharmaceuticals based on the azulene skeleton.
喹诺酮和喹啉衍生物经常作为药物活性化合物的子结构被发现。在本文中，我们描述了一种从2-芳基氨基薁衍生物合成薁并[2,1-]喹诺酮和喹啉的方法，该衍生物可通过2-氯薁衍生物与几种芳胺的芳香亲核取代反应轻松制备。薁并[2,1-]喹诺酮的合成是通过在五元环上带有两个酯基的2-芳基氨基薁衍生物的布朗斯特酸催化分子内环化反应实现的。用POCl对薁并[2,1-]喹诺酮进行卤化芳构化反应，得到在吡啶部分带有氯取代基的薁并[2,1-]喹啉。还研究了带有氯取代基的薁并[2,1-]喹啉与仲胺的芳香亲核取代反应，以得到氨基喹啉衍生物。本文报道的这些合成方法在基于薁骨架的新药物开发中应具有重要价值。
