近日，加拿大西蒙弗雷泽大学Robert Britton团队研究了核苷类似物合成的统一平台。相关论文于2026年3月5日发表在《科学》杂志上。

核苷类似物作为抗病毒和抗癌疗法的重要组成部分，其重要性不言而喻。尽管经过数十年的药物化学重点研究，但与之相关的化学空间仍未得到充分探索，这主要是由于其合成过程冗长且以单一分子为导向，缺乏生成核苷类似物库所需的灵活性。

研究组报道了一个利用光氧化还原偶联策略进行核苷类似物高通量合成的灵活、稳健且高效的平台。该方法能同时产生C-连接和N-连接的核苷类似物，并统一了包括4′-硫代、4′-亚氨基和ProTides前药在内的几类不同核苷类似物的合成路线，所有这些都源于一个简单且可规模化的中间体。利用该平台，研究组成功制备了多样化的核苷类似物库，并鉴定出若干具有抗HIV-1活性的先导化合物。他们期望这种合成核苷类似物的新方法能够激励并支持该领域的药物发现工作。

附：英文原文

Title: A unified platform for nucleoside analog synthesis

Author: Matthew J. Anketell, Ethan Fung, Wenbin Liu, Mahesh Shinde, Cyndi Qixin He, Kurtis W. C. Ng, Steven M. Silverman, Louis-Charles Campeau, Ralph Pantophlet, Robert Britton

Issue&Volume: 2026-03-05

Abstract: Nucleoside analogs (NAs) are essential as antiviral and anticancer therapies. Despite decades of focused medicinal chemistry efforts, their related chemical space remains underexplored, mainly due to their lengthy, single-molecule-oriented syntheses that lack the flexibility required to generate NA libraries. Here we report a flexible, robust, and efficient platform for the high-throughput synthesis of NAs using a photoredox coupling strategy. This approach produces both C- and N-linked NAs, and unifies the synthesis of several disparate NA classes, including 4′-thio, 4′-imino, and ProTides, all from a simple, scalable intermediate. Using this platform, we demonstrate the production of a diverse NA library and identify several hit compounds with anti-HIV-1 activity. We expect this new approach to NAs will inspire and support drug discovery efforts in this area.

DOI: aed6880

Source: https://www.science.org/doi/10.1126/science.aed6880