An Analysis of Published Synthetic Routes, Route Targets, and Reaction Types (2000–2020)

Abstract

Using a large data set (640k synthetic routes and 2.4m reactions) compiled from six popular journals between 2000 and 2020, trends are identified and discussed for topics including journal publishing rates, availability of machine-readable data, characteristics of synthetic route targets and starting materials (molecular weight, complexity, elemental composition, chirality, and ring systems), and the reaction classes utilized in these synthetic routes. We provide evidence of an ongoing shift away from large natural product or “total” syntheses among the academic data and a gradual increase in the size and complexity of industrial/medicinal target molecules. The reaction class analyses show key differences between the academic and industrial sectors and how a small number of reaction types have proliferated in the latter, giving rise to a possible lack of target diversity. Overall, there is evidence to support an ongoing increase in synthetic efficiency whereby, as a community, we are synthesizing larger, more-complex molecules from smaller, simpler starting materials, in fewer steps and with diminished reliance on nonproductive reaction types such as protecting group manipulations, redox reactions, and functional group interconversions.