Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry.
Cu(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition reaction in nucleoside, nucleotide, and oligonucleotide chemistry.
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DOI：
10.1021/cr9001462
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发表时间：
2009-09
期刊：
影响因子：
62.1
通讯作者：
Schinazi RF
中科院分区：
文献类型：
--
作者：
Amblard F;Cho JH;Schinazi RF
由 Huisgen 在 20 世纪 60 年代首创的乙炔和叠氮化物之间的 1, 1, 3-偶极环加成反应在 Sharpless 等人提出“点击化学”概念时重新引起人们的关注。这种方法基于较小单元的连接，模仿了自然界用来生成物质的方法。这一概念利用了模块化、范围广泛、立体定向和高产率的反应，并且仅产生无害性副产物，从而有效地获得新的有用化合物。此外，要完全“点击”，该过程必须涉及简单的反应条件、易于获得的起始材料和试剂、不使用溶剂、或良性或易于去除的溶剂。 3 起初，经典的 Huisgen 1, 3-偶极环加成不属于上述定义，但 Medal 和 Sharpless4 先后发现铜 (I) 盐催化该反应，使其从在恶劣条件下产生 1, 4- 和 1, 5- 区域异构体混合物的反应演变为可以在室温下在非常短的反应时间内进行的区域选择性反应（方案 1）。 Cu 炔烃-叠氮化物环加成 (CuAAC) 非常符合上述定义，以至于它几乎成为“点击化学”本身的同义词。事实上，CuAAC 可在多种溶剂中进行，包括水介质，再加上反应物的相对无害性，使其具有生物相容性。与其他金属催化反应相比，使用 Cu (I) 的主要优点是价格便宜且易于处理。（大多数方案涉及用钠盐还原稳定的 Cu (II) 源，例如 CuSO4，或 Cu (II)/Cu (0) 物质的比例化。）此外，炔烃和叠氮化物官能团都可以通过几种非常通用的方法掺入到各种化合物中，这一事实也可能有助于解释 Cu (II) 的广泛使用。该反应（方案 2 和 3）。 5 所有这些属性，再加上所得三唑的潜在有利的物理化学性质，推动 Cu (I) 催化的 Huisgen 环加成成为点击化学概念中最流行和最有效的反应之一；因此，过去几年有关该主题的出版物数量激增。在过去的 40 年里，药用核酸和核苷类似物的发展对应用于抗病毒和抗癌治疗的临床化疗产生了显着影响。例如，许多核苷类似物已成功开发用于治疗人类免疫缺陷病毒（HIV）、乙型肝炎病毒（HBV）、丙型肝炎病毒（HCV）、单纯疱疹病毒（HSV）、巨细胞病毒（CMV）或水痘带状疱疹病毒（VZV）（图1）和各种癌症（图2）。 6
Pioneered by Huisgen in the 1960s, 1 the 1, 3-dipolar cycloaddition reaction between acetylenes and azides was brought back into focus by Sharpless and others2 when they developed the concept of “click chemistry”. This approach, based on the joining of smaller units, mimics the approach used by nature to generate substances. This concept takes advantage of reactions that are modular, wide in scope, stereospecific, and high yielding and generate only nonoffensive byproducts to efficiently access new useful compounds. Moreover, to be completely “click”, the process must involve simple reaction conditions, readily available starting materials and reagents, the use of no solvent, or a benign or easily removable solvent. 3 At first, the classical Huisgen 1, 3-dipolar cycloaddition did not fall into the above definition, but the discovery of copper (I) salts catalyzing the reaction first by Medal and then by Sharpless4 allowed it to evolve from a reaction under harsh conditions that led to a mixture of 1, 4-and 1, 5-regioisomers to a regioselective reaction that can be performed at room temperature in very short reaction times (Scheme 1). The Cu alkyne-azide cycloaddition (CuAAC) fit so well into the above definition that it has become almost synonymous of “click chemistry” itself. Indeed, CuAAC proceeds in a variety of solvents, including aqueous media, which, combined with the relative innocuousness of the reactants, render it biocompatible. Compared to other metal-catalyzed reactions, the use of Cu (I) presents the major advantages of being inexpensive and easy to handle.(Most of the protocols involve the reduction of stable sources of Cu (II), such as CuSO4, with sodium salts or the comproportionation ofCu (II)/Cu (0) species.) In addition, the fact that both alkyne and azide functional groups can be incorporated into a wide range of compounds by several very general methods might also help explain the widespread use of this reaction (Schemes 2 and 3). 5 All these attributes, combined with the potentially favorable physicochemical properties of the resulting triazoles, have propelled the Cu (I)-catalyzed Huisgen cycloaddition to be one of the most popular and efficient reactions within the concept of click chemistry; as a result, a burst in the number of publications on the topic has occurred in a past few years. Over the last 40 years, the development of nucleic acids and nucleoside analogues for medicinal uses has had a marked impact on clinical chemotherapy as applied to antiviral and anticancer treatment. Numerous nucleoside analogues, for instance, were successfully developed for the treatment of human immunodeficiency viruses (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), cytomegalovirus (CMV), or varicella zoster virus (VZV)(Figure 1) and various cancers (Figure 2). 6
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