Rather recently, the same research group explored the ability of octahydroisochromene to interact with the hydrophobic S2 pocket as an innovative P2‐moiety. 150  To identify the best specific configuration, all possible diastereomers were evaluated. It was found that the molecule with (1S,3S)‐octahydroisochromene 53–56 could secure the optimal position of the P1‐imidazole as well as the aldehyde functional group at the active site. Additionally, the N‐butyl side chain attached to the 1‐position of the fused ring system was recognized to be important for establishing hydrophobic interactions.