The target molecules of the reference routes were subjected to prediction by the AiZynthFinder software . As stock we used the reference stock detailed in Section 2, i.e. all the leaves of the reference routes. We used no filter policy and the expansion policy was the one detailed above. As the search algorithm, we use an MCTS algorithm detailed previously, an implementation of the Retro* algorithm, or a depthfirst proof-number (DFPN) search. For Retro*, we used the official repository of the Retro* algorithm as a starting point, and re-implemented it in AiZynthFinder. An extension we implemented was continuing the search after the first solutions has been found and extraction of routes using the CompRet algorithm . For the DFPN, we started with the algorithm suggested by Kishimoto et al. . We used a constant unity edge cost, rewrote the algorithm to be iterative rather than recursive, and implemented logic similar to [27] to continue the search after the first solution has been found. Routes were extracted using the CompRet algorithm . Pseudo-code for all three search algorithms is provided in the Supporting Information. In all experiments, the search consisted of 500 iterations for MCTS and Retro*, 750 iterations for DFPN, and no time limits.