Enantioselective Total Synthesis of ROCK-inhibitor (S)-Netarsudil (Rhopressa) via Asymmetric Organocatalysis

Abstract

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