Convenient total synthesis of taranabant (MK-0364), a novel cannabinoid-1 receptor inverse agonist as an anti-obesity agent

Being obese has various health problems that are related to type 2 diabetes mellitus, cardiovascular disease, hypertension, hyperlipidemia, and fibrinolytic abnormalities. Merckʹs taranabant (MK-0364), a CB1R inverse agonist, is currently in Phase 3 clinical trials, and is being actively pursued by Merck toward obesity market. Merck intends to file for FDA approval of taranabant in 2008. In order to overcome practical difficulty involved in lab-scale preparation of taranabant with a dynamic kinetic resolution procedure developed by Merckʹs process group, we developed a ‘user-friendly’ method to install stereogenic centers by adopting Evans asymmetry chemistry. This method allowed us to prepare readily sub-gram scale of the target compound in a convenient way.