近日，格拉斯哥大学Leroy Cronin课题组在机器化学合成的研究中取得了新进展。 该研究于2020年12月22日发表于国际一流学术期刊《自然·化学》杂志上。

在该文中，研究人员展示了Chemputer合成机器人可以被编程以开展多种不同反应，包括固相肽合成、重复的交叉偶联反应，以及在单一、联合的系统中以高产率和纯度获得高反应性、不稳定的重氮甲烷。开发可使用同一自动化软件系统的普适、模块化硬件使开展各种各样的批量化学反应成为可能。该系统仅重复使用10个独特模块中的22个不同的步骤，通过编程17种反应的代码，可开展约8500次合成，验证了其普适性。

研究人员还展示了一个多肽与重氮甲烷反应的复杂汇聚化机器合成，该反应需要十二个合成步骤。

据了解，虽然自动化合成分子已被实现，但此前的报道中，每一类反应仍需定制特制的硬件。这意味着不太可能在同一机器中开展含许多不同反应方法的多步合成，因为替换硬件仍需人工操作。

附：英文原文

Title: Convergence of multiple synthetic paradigms in a universally programmable chemical synthesis machine

Author: Davide Angelone, Alexander J. S. Hammer, Simon Rohrbach, Stefanie Krambeck, Jarosaw M. Granda, Jakob Wolf, Sergey Zalesskiy, Greig Chisholm, Leroy Cronin

Issue&Volume: 2020-12-22

Abstract: Although the automatic synthesis of molecules has been established, each reaction class uses bespoke hardware. This means that the connection of multi-step syntheses in a single machine to run many different protocols and reactions is not possible, as manual intervention is required. Here we show how the Chemputer synthesis robot can be programmed to perform many different reactions, including solid-phase peptide synthesis, iterative cross-coupling and accessing reactive, unstable diazirines in a single, unified system with high yields and purity. Developing universal and modular hardware that can be automated using one software system makes a wide variety of batch chemistry accessible. This is shown by our system, which performed around 8,500 operations while reusing only 22 distinct steps in 10 unique modules, with the code able to access 17 different reactions. We also demonstrate a complex convergent robotic synthesis of a peptide reacted with a diazirine—a process requiring 12 synthetic steps.

DOI: 10.1038/s41557-020-00596-9

Source: https://www.nature.com/articles/s41557-020-00596-9