化学
共价键
电泳剂
位阻效应
硼酸
组合化学
胺气处理
螯合作用
药效团
有机化学
亲电取代
氨基酸
催化作用
立体化学
生物化学
作者
Di Ke,Lei Zhang,Xiuwen Zhong,Jiaan Shao,Yongping Yu,Wenteng Chen
出处
期刊:Organic Letters
[American Chemical Society]
日期:2022-02-05
卷期号:24 (6): 1263-1267
被引量:2
标识
DOI:10.1021/acs.orglett.1c03833
摘要
3,4-Hydroxypyridinone (3,4-HOPO) is a vital metal-chelating pharmacophore. However, the efficient synthesis has been a long-standing problem in drug development. In this paper, we report an efficient electrophilic activation of unprotected maltols via reversible covalent bonds between boronic acid and 3-hydroxyl/4-carbonyl. This one-pot reaction proceeded well on a gram scale in water with excellent efficiencies up to 97%. Moreover, taking advantage of the covalent interactions via the transient boronate, most of the previously tough amine donors, including sterically hindered amines, aromatic amines, and amino acids and amino alcohols, were well-tolerated. Importantly, the potential of this strategy in the pharmaceutical industry was highlighted with a successful synthesis of 3,4-HOPOs containing iron-chelating active pharmaceutical ingredients on 10 g and kilogram scales.
科研通智能强力驱动
Strongly Powered by AbleSci AI