SynthI: A New Open-Source Tool for Synthon-Based Library Design

Most of the existing computational
tools for de novo library design
are focused on the generation, rational selection, and combination
of promising structural motifs to form members of the new library.
However, the absence of a direct link between the chemical space of
the retrosynthetically generated fragments and the pool of available
reagents makes such approaches appear as rather theoretical and reality-disconnected.
In this context, here we present Synthons Interpreter (SynthI), a new open-source toolkit for de novo library design that allows
merging those two chemical spaces into a single synthons space. Here
synthons are defined as actual fragments with valid valences and special
labels, specifying the position and the nature of reactive centers.
They can be issued from either the “breakup” of reference
compounds according to 38 retrosynthetic rules or real reagents, after
leaving group withdrawal or transformation. Such an approach not only
enables the design of synthetically accessible libraries and analog
generation but also facilitates reagents (building blocks) analysis
in the medicinal chemistry context. SynthI code is publicly available
at https://github.com/Laboratoire-de-Chemoinformatique/SynthI.