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有机化合物和潜在候选药物的C-H氘代

C-H deuteration of organic compounds and potential drug candidates.

作者信息

Prakash Gaurav, Paul Nilanjan, Oliver Gwyndaf A, Werz Daniel B, Maiti Debabrata

机构信息

Department of Chemistry, IIT Bombay, Powai, Mumbai-400076, India.

Technische Universität Braunschweig, Institute of Organic Chemistry, Hagenring 30, 38106 Braunschweig, Germany.

出版信息

Chem Soc Rev. 2022 Apr 19;51(8):3123-3163. doi: 10.1039/d0cs01496f.

Abstract

C-H deuteration has been intricately developed to satisfy the urgent need for site-selectively deuterated organic frameworks. Deuteration has been primarily used to study kinetic isotope effects of reactions but recently its significance in pharmaceutical chemistry has been discovered. Deuterium labelled compounds have stolen the limelight since the inception of the first FDA-approved deuterated drug, for the treatment of chorea-associated Huntington's disease, and their pharmacological importance was realised by chemists, although surprisingly very late. Various approaches were developed to carry out site-selective deuteration. However, the most common and efficient method is hydrogen isotope exchange (HIE). This review summarises deuteration methods of various organic motifs containing C(sp)-H and C(sp)-H bonds utilizing C-H bond functionalisation as a key step along with a variety of catalysts, and exemplifies their biological relevance.

摘要

碳-氢氘代技术已得到深入发展,以满足对位点选择性氘代有机骨架的迫切需求。氘代主要用于研究反应的动力学同位素效应,但最近人们发现了它在药物化学中的重要性。自首款获得美国食品药品监督管理局(FDA)批准的用于治疗与舞蹈症相关的亨廷顿氏病的氘代药物问世以来,氘标记化合物备受关注,尽管令人惊讶的是,化学家们很晚才意识到它们的药理学重要性。人们开发了各种方法来进行位点选择性氘代。然而,最常用且高效的方法是氢同位素交换(HIE)。本综述总结了利用碳-氢键官能化作为关键步骤,借助各种催化剂对含有C(sp)-H和C(sp²)-H键的各种有机基团进行氘代的方法,并举例说明了它们的生物学相关性。

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