Ensitrelvir

A practical route to Ensitrelvir: The unprecedented strategy utilizing a meta-cresolyl moiety enhanced the stability of intermediate compounds and enabled scalable manufacturing of 1. The 6-step longest linear sequence (from 26) delivers the target molecule in 35.1% yield. This overall yield was improved by approximately 7-fold compared to the earlier process used in the early research and development stage (4.8%). Our convergent approach to the synthesis of 1 made the manufacturing process concise, streamlined, and short. Direct crystallization was achieved in 9 out of the 12 steps, thus establishing a greener process without silica-gel column chromatographic purification. In addition, the present practical process settled all the issues that made large-scale synthesis difficult, i.e., removal of corrosive acid by evaporation and the generation of noxious odors from thiol derivatives.^[2]

The U.S. Food and Drug Administration (FDA) granted Fast Track designation to Ensitrelvir for COVID-19. FDA Fast Track designation is designed to facilitate the development and expedite the review of potential new therapies that treat severe conditions and fulfill an unmet medical need. Ensitrelvir was approved in Singapore in November 2023 based on the Special Access Route application. Ensitrelvir remains an investigational drug outside of Japan and Singapore. In addition, the brand name Xocova? has not been approved for use outside of Japan and Singapore and pertains only to the approved drug in Japan and Singapore.