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离子液体中核苷的结构修饰。

Structural modifications of nucleosides in ionic liquids.

机构信息

Laboratory of Synthetic Chemistry, SAIC -Frederick Inc., National Cancer Institute at Frederick, 1050 Boyles St., Frederick, MD 21702, USA.

出版信息

Biochimie. 2010 Sep;92(9):1260-5. doi: 10.1016/j.biochi.2010.02.019. Epub 2010 Feb 21.

Abstract

Nucleoside chemistry represents an important research area for drug discovery, as many nucleoside analogs are prominent drugs and have been widely applied for cancer and viral chemotherapy. However, the synthesis of modified nucleosides presents a major challenge, which is further aggravated by poor solubility of these compounds in common organic solvents. Most of the currently available methods for nucleoside modification employ toxic high boiling solvents; require long reaction time and tedious workup methods. As such, there is constant effort to develop process chemistry in alternative medium to limit the use of organic solvents that are hazardous to the environment and can be deleterious to human health. One such approach is to use ionic liquids, which are 'designer materials' with unique and tunable physico-chemical properties. Studies have shown that methodologies using ionic liquids are highly efficient and convenient for the synthesis of nucleoside analogs, as demonstrated by the preparation of pharmaceutically important anti-viral drugs. This article summarizes recent efforts on nucleoside modification using ionic liquids.

摘要

核苷化学是药物发现的一个重要研究领域,因为许多核苷类似物是重要的药物,并已广泛应用于癌症和病毒性化疗。然而,修饰核苷的合成是一个主要的挑战,而这些化合物在常见有机溶剂中的低溶解度进一步加剧了这一挑战。目前大多数用于核苷修饰的方法都使用有毒的高沸点溶剂;需要长时间的反应时间和繁琐的后处理方法。因此,人们一直在努力开发替代介质中的过程化学,以限制使用对环境有害且可能对人类健康有害的有机溶剂。一种这样的方法是使用离子液体,它是具有独特和可调物理化学性质的“设计材料”。研究表明,离子液体方法对于核苷类似物的合成非常高效和方便,这已通过制备具有重要药用价值的抗病毒药物得到证明。本文总结了使用离子液体进行核苷修饰的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6799/3214640/3dd9956108e3/nihms181331f1.jpg

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本文引用的文献

1
Ionic liquid mediated synthesis of 5-halouracil nucleosides: key precursors for potential antiviral drugs.
Nucleosides Nucleotides Nucleic Acids. 2009 Sep;28(9):821-34. doi: 10.1080/15257770903170252.
3
Synthesis of nucleoside-based antiviral drugs in ionic liquids.离子液体中基于核苷的抗病毒药物的合成。
Bioorg Med Chem Lett. 2008 Oct 15;18(20):5640-2. doi: 10.1016/j.bmcl.2008.08.090. Epub 2008 Aug 29.
5
L-nucleoside enantiomers as antivirals drugs: a mini-review.L-核苷对映体作为抗病毒药物:一篇综述
Antiviral Res. 2006 Sep;71(2-3):276-81. doi: 10.1016/j.antiviral.2006.04.017. Epub 2006 May 23.
8
Recent highlights in the development of new antiviral drugs.新型抗病毒药物研发的近期亮点。
Curr Opin Microbiol. 2005 Oct;8(5):552-60. doi: 10.1016/j.mib.2005.08.010.

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