An analysis of published synthetic routes, route targets and reaction types (2000 – 2020)

Using a large dataset (640k synthetic routes and 2.4m reactions) compiled from six popular journals between 2000 – 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 utilised in these synthetic routes. We provide evidence of an ongoing shift away from large natural product or “total” syntheses amongst 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 non-productive reaction types such as protecting group manipulations, redox reactions and functional group interconversions.