韩国蔚山科技大学Bartosz A. Grzybowski等研究人员合作实现复杂天然产物合成的计算机设计。这一研究成果于2020年10月13日在线发表在国际学术期刊《自然》上。

研究人员表示，教会计算机来计划多步有机合成已成为50多年来的挑战。自从早期的开创性贡献以来，包括诸如LHASA之类的程序（由操作员在每个步骤做出反应选择），该领域取得了长足的进步，现在有多个软件平台可以完全自主地进行规划。不过，这些程序一次只能“思考”一次，并且到目前为止仅限于相对简单的目标，可以说，它们的合成可以由人类化学家在几分钟内无需计算机的帮助下进行设计。迄今为止，还没有一种算法能够设计出通向复杂天然产物的合理路线，为此，必须进行复杂的多步计划，并且不能依靠紧密相关的文献先例。

研究人员证明了这样的路线选择是可行的，假如这一机器对有机化学和基于数据的人工智能程序的了解与因果关系得以增强，从而使其能够在多个合成步骤上制定策略。通过这些改进，对合成专家进行的类似图灵测试的结果表明，计算机设计的路线与人类设计的路线在很大程度上没有区别。在实验室中成功验证了三种计算机设计的天然产物合成物。综上所述，这些结果表明，专家级的自动综合计划最终将变得可行，但这需要对反应知识基础的不断改进和进一步的代码优化。

附：英文原文

Title: Computational planning of the synthesis of complex natural products

Author: Barbara Mikulak-Klucznik, Patrycja Gobiowska, Alison A. Bayly, Oskar Popik, Tomasz Klucznik, Sara Szymku, Ewa P. Gajewska, Piotr Dittwald, Olga Staszewska-Krajewska, Wiktor Beker, Tomasz Badowski, Karl A. Scheidt, Karol Molga, Jacek Mynarski, Milan Mrksich, Bartosz A. Grzybowski

Issue&Volume: 2020-10-13

Abstract: Teaching computers to plan multistep organic syntheses has been a challenge for over 50 years1–7. Since early pioneering contributions, including programs such as LHASA1,7 (with reaction choices at each step made by human operator), the field has progressed greatly and there are now multiple software platforms6,8–13 capable of completely autonomous planning. Still, these programs ‘think’ only one step at a time and have so far been limited to relatively simple targets whose syntheses could, arguably, be designed by human chemists within minutes and without computer’s help. To date, no algorithm has been able to design plausible routes to complex natural products for which significantly more far-sighted, multi-step planning is necessary14,15 and for which one cannot rely on closely related literature precedents. Here we demonstrate that such route choices are possible, provided that the machine’s knowledge of organic chemistry and data-based artificial intelligence routines are augmented with causal relationships16,17, allowing it to strategize over multiple synthetic steps. With these improvements, results of a Turing-like test administered to synthesis experts indicate that the routes designed by computer become largely indistinguishable from those designed by humans. Three computer-designed syntheses of natural products were successfully validated in the lab. Taken together, these results indicate that automated synthetic planning at an expert level is finally becoming feasible, pending continued improvements to the reaction-knowledge base and further code optimization.

DOI: 10.1038/s41586-020-2855-y

Source: https://www.nature.com/articles/s41586-020-2855-y