Catalysis is increasingly important in the pharmaceutical industry for the development of cost-effective and eco-friendly drug manufacturing processes. Merck Process Research & Development has a long history of catalysis innovation and continues to focus on applications of novel catalytic transformations for the synthesis of active pharmaceutical ingredients at all stages of development. This presentation will highlight two stories about the design and development of biocatalytic and chemocatalytic processes for the synthesis of antiviral agents EFdA and vaniprevir. The first part will include the discovery of a synthetic route that utilized a biocatalytic desymmetrization for an expedient multi-kilogram synthesis of EFdA to enable first in human (FIH) clinical studies, as well as recent ongoing work toward the development of a more cost-effective and innovative manufacturing route. In the second part, chemocatalytic process development for the HCV therapeutic vaniprevir will be presented, including an efficient construction of the 20-membered macrocylic core of vaniprevir utilizing ring-closing metathesis technology and the serendipitous discovery of a new metathesis catalysts from our synthetic efforts toward the HCV therapeutic grazoprevir (MK-5172).

Design and development of catalytic processes for the synthesis of antiviral agents EFdA (MK-8591) and vaniprevir (MK-7009)

2019 Fall National Meeting

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