Planning of multistep syntheses leading to complex targets is often a creative but also a difficult and time-consuming process. Chemists were among the pioneers of using computers in various research tasks and, in particular, have strived for over five decades now to teach the machines the art of synthetic design. However, despite numerous and often ingenious approaches being pursued, there have been no examples of syntheses of non-trivial targets first planned by the machine and then successfully executed in the laboratory. With enormous improvements in computers’ performance, with the modern methods of machine learning and graph theory, and with carefully encoded reaction mechanisms, our team has been able to develop the so-called Chematica platform that is finally capable of completely automated and chemically correct design of synthetic pathways leading to arbitrary targets, including complex natural products. In my talk, I will first discuss the theoretical basis of the program that emerged over many years of concerted effort, and then talk about its all-important validation in which this software designed, without human supervision, syntheses leading to numerous targets diverse both in terms of structure and complexity – these computer designed routes were later executed in the laboratory and in all cases offered significant improvements over previous approaches or identified efficient routes to targets for which previous synthetic attempts proved unsuccessful. With these results documenting the ability of machines to creatively apply known reaction types/mechanisms, I will also discuss their ability to discover completely *new* synthetic knowledge (ranging from previously unreported tactical combinations to new reaction types). Integration of such computer-driven discovery into mainstream synthetic effort appears an exciting opportunity – and a challenge – for the organic-synthetic research in the years to come.

Chematica: Computer-planned syntheses of natural products and their experimental execution

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.