Abstract Body: Non-adherence is a major hurdle for the effective treatment of HIV, a global epidemic even after 30 years of medical advancements. Long-acting therapeutics have the potential to improve adherence through simplified regimens. One such investigational medication is MK-8591, a nucleoside reverse transcriptase translocation inhibitor with subnanomolar antiviral activity and a long intracellular half-life. To support this program, a world-class manufacturing synthesis which is robust, green, and sustainable was targeted. In this presentation, I will describe how our team has addressed the long standing challenge of stereoselective glycosylation with a novel three-enzyme biocatalytic cascade. I will also discuss the multiple routes developed to efficiently complete the synthesis, and the novel catalytic methods which enabled each route. Highlights include two new methods for enantioselective ketone alkynylation, and a route consisting of nine enzymes across three steps.

Aaron Whittaker received his Ph.D. in 2013 at the University of Washington under the supervision of Prof. Gojko Lalic where he developed new copper-catalyzed methods for hydroamination, aryl amination, allylic substitution, semi-reduction, and hydrodefluorination. Upon receiving his Ph.D, Aaron moved to the University of California, Irvine as a postdoctoral associate with Prof. Vy Dong where he developed nickel-catalyzed transfer hydrogenations. Since 2015, Aaron has been a process chemist at Merck where he focuses on developing new methods, and robust synthetic routes to enable large scale synthesis of complex drug molecules.