The enantioselective total synthesis of ROCK-inhibitor ( <i>S</i> )-Netarsudil (Rhopressa) <i>via</i> asymmetric organocatalysis

A new efficient and waste-free approach to synthesize (<i>S</i>)-Netarsudil, a blockbuster drug for the treatment of glaucoma and increased intraocular pressure (IOP), has been developed. It is based on the use of terephthalic dialdehyde as a commercially available starting compound and an asymmetric organocatalytic Michael reaction as the key step responsible for the creation of a stereogenic center with the required (<i>S</i>)-configuration. The advantages of the proposed methodology over the currently known one are the higher overall yield of the target drug, use of a reusable organocatalyst, mild and green reaction conditions, and the elimination of labor-intensive and time-consuming stages for the isolation of auxiliary groups.