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Cu催化不对称环化从头合成手性氨基吲哚及磺胺酰基迁移的发现
作者:小柯机器人 发布时间:2022/10/25 9:54:27

华中师范大学陆良秋团队报道了Cu催化不对称环化从头合成手性氨基吲哚及磺胺酰基迁移的发现。相关研究成果发表在2022年10月21日出版的国际学术期刊《美国化学会杂志》。

寻找获得结构新颖的氨基吲哚类药物的有效策略对药物发现具有重要意义。然而,具有多样化功能的氨基吲哚啉支架的催化不对称从头构建仍然难以实现。

该文中,研究人员报道了铜催化的乙炔基苯并恶嗪酮与胺的不对称环化反应,以良好的产率和高的对映选择性(高达97%产率和98:2er)生产手性3-氨基吲哚。此外,意外地发现了这些产物的自由基介导的磺酰基迁移,进一步提供了新的手性3-氨基吲哚,其具有保留的对映体纯度(高达84%产率和98:2er)。生物活性评估表明,这些3-氨基吲哚类化合物显示出显著的抗肿瘤活性,其手性对其抗肿瘤活性有显著影响。

附:英文原文

Title: De Novo Construction of Chiral Aminoindolines by Cu-Catalyzed Asymmetric Cyclization and Subsequent Discovery of an Unexpected Sulfonyl Migration

Author: Bao-Cheng Wang, Tingting Fan, Fen-Ya Xiong, Peng Chen, Kai-Xin Fang, Ying Tan, Liang-Qiu Lu, Wen-Jing Xiao

Issue&Volume: October 21, 2022

Abstract: Searching for efficient strategies to access structurally novel aminoindolines is of great significance for drug discovery. However, catalytic asymmetric de novo construction of aminoindoline scaffolds with functionality primed for diversification still remains elusive. Here, we report a Cu-catalyzed asymmetric cyclization of ethynyl benzoxazinones with amines, producing chiral 3-aminoindolines in good yield and with high enantioselectivity (up to 97% yield and 98:2 er). Moreover, a radical-mediated sulfonyl migration of these products was unexpectedly found, further affording new chiral 3-aminoindolines bearing alkenyl sulfonyl groups with retained enantiopurity (up to 84% yield and 98:2 er). Bioactivity evaluations indicate that these 3-aminoindolines show notable antitumor activities and chirality is proven to have a significant impact on their antitumor activity.

DOI: 10.1021/jacs.2c08090

Source: https://pubs.acs.org/doi/10.1021/jacs.2c08090

 

期刊信息

JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:14.612
官方网址:https://pubs.acs.org/journal/jacsat
投稿链接:https://acsparagonplus.acs.org/psweb/loginForm?code=1000