19 July 2021

Poll results: synthetic challenges are pervasive in FBLD

Last month we wrote about “sociable” vs “unsociable” fragments: the former are amenable to straightforward chemistry for fragment growing, merging, or linking, while the latter are not. This categorization prompted a poll on how often synthetic challenges have kept you from pursuing a particular fragment or impeded a fragment-to-lead project. The results are now in.
(Methods note: the poll was run on Crowdsignal from 14 June through 16 July. There were 42 responses to the first question and 44 to the second. Respondents came from a dozen countries with the most from the US, UK, Germany, Denmark, Netherlands, Australia, France, and Italy.)
Responses were similar for both questions: a fifth to a quarter of respondents often found that synthetic challenges kept them from pursuing a particular fragment or impeded work on a fragment-to-lead project, nearly half sometimes found this to be the case, while a fifth to a third rarely experienced this. Only a handful of people never found synthetic challenges limiting.
It is heartening that around a third of respondents are rarely if ever impeded by chemistry, perhaps because they have intentionally constructed their libraries with sociable fragments. Still, the fact that nearly two thirds of researchers sometimes or often run into problems suggests a continuing need for synthetically enabling fragment chemistry.
For academic chemists looking to make a practical impact, this could be a fertile area. And fragment library vendors looking to differentiate themselves may want to consider providing robust synthetic routes and methodologies for their available compounds.