加拿大西蒙弗雷泽大学Robert Britton小组在最新研究中，实现了核苷类似物的简单从头合成。2020年8月7日出版的《科学》杂志发表了这一成果。

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