After the experiment, we compared the five methods listed in Table . As mentioned above, for the vanilla SMC, the design of the single-chain reaction routes was tested under three different step sizes n ∈ {1, 2, 3}. Therefore, seven methods were included in this comparison. Each method was tested in two scenarios. In scenario 1, a relatively small number of commercial compounds was assumed to be available: the candidate reactants were generated by randomly sampling 10k of the 150k Enamine compounds available for purchase. In scenario 2, all 150k compounds were used to design the molecules. First, we report the results of scenario 1. As a performance measure, we simply considered the number of unique designed molecules that reached the target property range. Figure shows the evolution of the number of unique hit molecules at each step of the sequential calculation. Unsurprisingly, the two random search algorithms were clearly less efficient than the others. For SMC-1 and Random, whose design space is restricted to single-step reactions with two reactants, the number of hits decayed as the number of search steps increased. This means that the limited design space consisting of two combinations of at-most 10k commercial compounds can be adequately covered by the naive algorithms. In contrast, for the vanilla SMC with two-and three-step reactions (SMC-2, SMC-3) and the recurrent algorithms to explore arbitrary reaction networks (SMC-RECUR-GTM, SMC-RECUR-GTM-SR-PL), the number of hit molecules at each step remained constant, and no decay trend was observed for T = 10000. This observation confirms that the search space for general reaction design is quite large. In the comparison between SMC-RECUR-GTM and its extended version, SMC-RECUR-GTM-SR-PL with the surrogate models shows that the number of hits of the latter is slightly lower than that of the former. This is a natural consequence because the surrogate models involve approximation errors. where the number of commercially available reactants is limited to 10K. The correspondence between the seven methods and their labels is shown in Table .