ABSTRACT: Nucleoside analogues are ubiquitous in nature and are critical component of life-saving therapies used in the treatment of viral disease and cancer. Despite their widespread use and commercial value, the state-of-the-art methods for their preparation in drug discovery, drug development and eventual commercialization are lacking and remain a poorly solved problem in organic synthesis. In addition to posing synthetic challenges, custom nucleoside total synthesis presents several challenges with respect to green and sustainable chemistry, where current methods largely rely on chiral pool feedstocks and protecting group chemistry. We have developed a suite of novel methods for the synthesis and scale-up of nucleosides, as exemplified by the synthesis of Islatravir for the treatment of HIV infection. These efforts have culminated in an aspirational synthesis from commodity chemicals using a biocatalytic in-vitro cascade for construction of the nucleoside.
BIO: Dr. Campeau obtained his Ph. D. degree in 2008 with the late Professor Keith Fagnou at the University of Ottawa in Canada as an OGSST & NSERC post-graduate scholar, after completing his B.Sc. in Biopharmaceutical Sciences. He first joined Merck Research Laboratories at Merck-Frosst in Montreal in 2007. During his tenure at Merck-Frosst, L.-C. amassed several accomplishments, including key contributions to the discovery of Doravirine (approved in 2018 by the FDA and marketed as Delstrigo and Pifeltro). In 2010, he moved from Montreal to New Jersey, where he has served in roles of increasing responsibility ever since. After his roles as Director and Head of the Catalysis and Automation Laboratory and then Director in Process Chemistry, where he led teams through very challenging assignments on manufacturing route development, L.-C. was appointed Executive Director. He is currently the Head of Process Chemistry and Discovery Process Chemistry organizations, leading a team of >90 smart creative scientists developing innovative chemistry solutions in support of all pre-clinical and clinical active pharmaceutical ingredient deliveries for the entire Merck portfolio for small-molecule therapeutics. L.C.’s passion for scientific excellence is exemplified by >60 publications and patents, several successful collaborations with key academics, and an extensive list of invited lectures worldwide.