A short de novo synthesis of nucleoside analogs

doi:10.1126/science.abb3231

GSTDTAP > 气候变化

DOI	10.1126/science.abb3231
	A short de novo synthesis of nucleoside analogs
	Michael Meanwell; Steven M. Silverman; Johannes Lehmann; Bharanishashank Adluri; Yang Wang; Ryan Cohen; Louis-Charles Campeau; Robert Britton
	2020-08-07
发表期刊	Science
出版年	2020
英文摘要	Nucleotide analogs are valuable tools and therapeutics because of their ability to interfere with processes such as DNA synthesis, which are vital to rapidly dividing cells and replicating viruses. These molecules are challenging to synthesize chemically. Meanwell et al. developed a “ribose last” synthetic strategy in which a fluorinated acyclic nucleic acid is formed by an l- or d-proline–catalyzed aldol reaction (see the Perspective by Miller). This intermediate can then be cyclized to yield the nucleic acid analog in one pot with control of anomeric conformation based on cyclization conditions. Nucleotide analogs accessible by this strategy include those with modifications at C2′ and C4′, purines and pyrimidines, and locked and protected products. Science , this issue p. [725][1]; see also p. [623][2] Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of d- or l-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development. [1]: /lookup/doi/10.1126/science.abb3231 [2]: /lookup/doi/10.1126/science.abd1283
领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/288026
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Michael Meanwell,Steven M. Silverman,Johannes Lehmann,et al. A short de novo synthesis of nucleoside analogs[J]. Science,2020.
APA	Michael Meanwell.,Steven M. Silverman.,Johannes Lehmann.,Bharanishashank Adluri.,Yang Wang.,...&Robert Britton.(2020).A short de novo synthesis of nucleoside analogs.Science.
MLA	Michael Meanwell,et al."A short de novo synthesis of nucleoside analogs".Science (2020).