两步法合成复杂人工大环化合物。
Two-Step Synthesis of Complex Artificial Macrocyclic Compounds.
机构信息
Drug Design, University of Groningen, Address Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Chemistry Department, Faculty of Science, Sohag University, Sohag, 82524, Egypt.
出版信息
Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10725-10729. doi: 10.1002/anie.201704426. Epub 2017 Aug 1.
Abstract
The design and synthesis of head-to-tail linked artificial macrocycles using the Ugi-reaction has been developed. This synthetic approach of just two steps is unprecedented, short, efficient and works over a wide range of medium (8-11) and macrocyclic (≥12) loop sizes. The substrate scope and functional group tolerance is exceptional. Using this approach, we have synthesized 39 novel macrocycles by two or even one single synthetic operation. The properties of our macrocycles are discussed with respect to their potential to bind to biological targets that are not druggable by conventional, drug-like compounds. As an application of these artificial macrocycles we highlight potent p53-MDM2 antagonism.
摘要
已经开发出使用 Ugi 反应设计和合成头尾相连的人工大环。这种仅两步的合成方法是前所未有的，简短、高效且适用于广泛的中（8-11）环和大环（≥12）环大小。底物范围和官能团耐受性非常出色。使用这种方法，我们通过两步甚至一步单一合成操作合成了 39 个新的大环。我们讨论了大环的性质，以及它们与不能被传统类似药物化合物成药的生物靶标结合的潜力。作为这些人工大环的应用，我们强调了有效的 p53-MDM2 拮抗作用。
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