Computer-aided key step generation in alkaloid total synthesis
Computer-aided key step generation in alkaloid total synthesis
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DOI：
10.1126/science.ade8459
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发表时间：
2023-02-03
期刊：
影响因子：
56.9
通讯作者：
Cernak, Tim
中科院分区：
文献类型：
--
作者：
Lin, Yingfu;Zhang, Rui;Cernak, Tim
高效的化学合成对于满足未来对药物、材料和农用化学品的需求至关重要。几十年来，对不太复杂的分子的逆向合成分析已经实现了自动化，但直到最近，路线可能性的组合爆炸才对计算机硬件和软件构成了挑战。在这里，我们探索了一种计算策略，将计算机辅助合成计划与分子图编辑相结合，以最大限度地减少生产生物碱所需的合成步骤数量。我们的研究最终通过利用高影响的关键步骤对映体选择性地合成(-)-司他莫胺三步，这些步骤可以在使用图形编辑距离的计算机生成的逆合成计划中确定。
Efficient chemical synthesis is critical to satisfying future demands for medicines, materials, and agrochemicals. Retrosynthetic analysis of modestly complex molecules has been automated over the course of decades, but the combinatorial explosion of route possibilities has challenged computer hardware and software until only recently. Here, we explore a computational strategy that merges computer-aided synthesis planning with molecular graph editing to minimize the number of synthetic steps required to produce alkaloids. Our study culminated in an enantioselective three-step synthesis of (-)-stemoamide by leveraging high-impact key steps, which could be identified in computer-generated retrosynthesis plans using graph edit distances.