库尔提乌斯重排反应：在现代药物发现和药物化学中的应用。
The Curtius Rearrangement: Applications in Modern Drug Discovery and Medicinal Chemistry.
机构信息
Department of Chemistry and Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
出版信息
ChemMedChem. 2018 Nov 20;13(22):2351-2373. doi: 10.1002/cmdc.201800518. Epub 2018 Oct 11.
Abstract
The Curtius rearrangement is the thermal decomposition of an acyl azide derived from carboxylic acid to produce an isocyanate as the initial product. The isocyanate can undergo further reactions to provide amines and their derivatives. Due to its tolerance for a large variety of functional groups and complete retention of stereochemistry during rearrangement, the Curtius rearrangement has been used in the synthesis of a wide variety of medicinal agents with amines and amine-derived functional groups such as ureas and urethanes. The current review outlines various applications of the Curtius rearrangement in drug discovery and medicinal chemistry. In particular, the review highlights some widely used rearrangement methods, syntheses of some key agents for popular drug targets and FDA-approved drugs. In addition, the review highlights applications of the Curtius rearrangement in continuous-flow protocols for the scale-up of active pharmaceutical ingredients.
摘要
Curtius 重排反应是羧酸衍生的酰基叠氮化物在热作用下分解，生成异氰酸酯作为初始产物。异氰酸酯可以进一步反应，提供胺及其衍生物。由于其对多种官能团的耐受性以及在重排过程中立体化学的完全保留，Curtius 重排反应已被广泛应用于合成具有胺和胺衍生官能团的各种药物，如脲和尿烷。本综述概述了 Curtius 重排反应在药物发现和药物化学中的各种应用。特别是，该综述强调了一些广泛使用的重排方法，用于合成一些针对热门药物靶点和 FDA 批准药物的关键试剂。此外，该综述还强调了 Curtius 重排反应在活性药物成分的连续流动方案中的应用，以实现规模放大。
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