科學家實現核苷類似物的簡單從頭合成
作者：
小柯機器人發布時間：2020/8/7 12:58:39
加拿大西蒙弗雷澤大學Robert Britton小組在最新研究中，實現了核苷類似物的簡單從頭合成。2020年8月7日出版的《科學》雜誌發表了這一成果。
研究人員提出了一種從簡單的非手性材料快速構建核苷類似物的過程。僅使用脯氨酸催化，將雜芳基取代的乙醛進行氟化，然後在單鍋反應中直接參與對映選擇性羥醛反應。隨後的分子內氟化物置換反應提供了官能化的核苷類似物。在D-或L-核苷類似物、選定的核酸、亞氨基核苷以及C2'-和C4'-修飾的核苷類似物的多譜合成中突出了該過程的多功能性。
這種從頭開始的合成為製備多樣性文庫創造了機會，並將支持藥物的發現和開發。
據介紹，核苷類似物通常用於治療癌症和病毒感染。它們的合成得益於數十年來的研究，但往往耗時、無法多樣化，並且依賴於手性碳水化合物原料的儲備。
附：英文原文
Title: A short de novo synthesis of nucleoside analogs
Author: Michael Meanwell, Steven M. Silverman, Johannes Lehmann, Bharanishashank Adluri, Yang Wang, Ryan Cohen, Louis-Charles Campeau, Robert Britton
Issue&Volume: 2020/08/07
Abstract: 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.
DOI: 10.1126/science.abb3231
Source: https://science.sciencemag.org/content/369/6504/725
Science：《科學》，創刊於1880年。隸屬於美國科學促進會，最新IF：41.037