Inspired by Lavigne et al. we study an important step of the synthesis of Berkelyone A reported by Elkin et al. (Figure ). We choose the same protonated epoxide reactant structure as Lavigne et al. for the starting point of our analysis (Figure ). In practice several protonation sites must be investigated but this process can easily be automated. Figure highlights some pathways found using meta-MD for product generation and RMSD-PP for barrier estimates at the GFN2-xTB level. As our goal with this example is to check the ability of meta-MD + RMSD-PP to give insight into more complicated multi-step reactions compared to the elementary reactions studied until now we skip the DFT validation step and report the GFN2-xTB energies and barrier estimates. Thus, the energetics presented in Figure are not expected to be quantitatively accurate. Doing meta-MD + RMSD-PP starting from the reactant structure (R) produces reactions involving ring-opening of the protonated epoxide to produce both secondary and tertiary carbocations, proton transfer from the epoxide to the carbonyl oxygen of the ester group, as well as tautomerization reactions. Instead of restarting the procedure from every one of the produced intermediates, we choose to follow the path involving the tertiary carbocation I1 further. Continuing this process we create reaction profiles as presented in Figure . We locate a possible mechanism for the path to the product (P) through the five steps connected in black. We also show a pathway to one of the other (less stable) stereoisomers of the product (Pa, blue) as well as the path to the most stable product encountered (Pb, purple). We note that both the intermediate I2 and Pb is also found in the study conducted by Lavigne et al. We also find paths to macrocycle structures (from I1) which is also found by them. The most stable intermediate (I2), a bicyclic ether, is a known byproduct when doing this type of epoxide-initiated cyclizations. The competition between carbon cyclisation (P) and oxygen cyclisation (Pb) is also a known problem for these reactions.