Improved Laboratory Synthesis of YC-071, a Potent Azole Antifungal Agent

Abstract

An improved laboratory synthesis of YC-071, a potent azole antifungal agent, has been developed. Compared with the original route, the new route is operationally simple, requiring only limited purification of all the intermediates. The new route is an important scalable synthesis, which meets the need for YC-071 for use in preclinical studies.

Asymmetric Catalytic Epoxidation of Terminal Enones for the Synthesis of Triazole Antifungal Agents

“…Similarly, the potential bioactive species i-5 and i-6 could be provided by a ring-opening reaction of epoxide i-3 with 1-(2-(4-fluoro­phenoxy)­ethyl)­piperazine and 2-(3,4-dimethoxy­phenyl)- N -methylethan-1-amine separately (Scheme ). Moreover, after a nucleophilic ring-opening reaction of the epoxide with sodium azide, catalytic hydrogenation under a hydrogen atmosphere gave the vicinal amino alcohol i-7 with maintained enantioselectivity, the key intermediate for the synthesis of albaconazole and YC-071 . As a result, these antifungal agents shown in Scheme could be available through the new asymmetric synthetic route.…”