Sitagliptin Manufacture: A Compelling Tale of Green Chemistry, Process Intensification, and Industrial Asymmetric Catalysis

摘要

Process chemistry is a challenging science. Not only do the practitioners have to make the target molecule efficiently, but they also have to contend with numerous other equally (and often times more) important considerations such as process safety, waste streams, chemical toxicity, recycling of solvents/catalysts,process economics, and a multitude of engineering/technology considerations.Nevertheless, despite the challenges, the ideal outcome of these efforts when accomplished is quite satisfying: a simple, efficient, green, robust, and safe manufacturing process.Sitagliptin is the active ingredient in Januvia, a leading drug for the treatment of type 2 diabetes. Researchers from Merck, in collaboration with those from Solvias and Codexis, have recently reported on their process research and development efforts towards the industrial manufacture of sitagliptin phosphate (1). A showcase of green chemistry, process intensification, and industrial asymmetric catalysis-the sitagliptin manufacture has garnered wide acclaim. More importantly, it has served as a vehicle for discovery in organic synthesis. This highlight will focus on the evolution of the sitagliptin manufacture through three generations of process research and development.