Development of a practical and scalable synthesis of anti-HBV drug Y101

The process research and development of a practical and scalable synthetic method towards Anti-HBV Drug N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) was described. Initial synthetic routes of Y101 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the collaboration between Medicinal Chemistry and Research active pharmaceutical ingredient (API), a fit for purpose route for the kilo scale synthesis of Y101 was developed. In contrast, the improved route described here did not require purification by column chromatography for all steps, and the formation of impurities was effectively suppressed. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of Y101.

We have developed a safe, practical and reproducible process for the first fully synthetic Anti-HBV drug N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101) to allow preclinical and clinical development (see picture). Several kilograms of active pharmaceutical ingredient have been manufactured by this process to date. This material has been sufficient to provide for development as well as drug product manufacturing for early clinical studies.