Pemafibrate is a potent and selective agonist of peroxisome proliferator-activated receptor alpha (PPARα). It was designed to improve lipid metabolism with enhanced safety and efficacy compared to traditional fibrates and is clinically approved in Japan to treat hyperlipidemia. This strong PPARα agonist is also widely used in academic research to study various metabolic and cardiovascular disorders. However, the very high commercial cost can limit academic studies when gram-scale quantities are required or when structural modifications are being explored en route to novel applications. In this work, convenient and high-yielding laboratory-scale procedures are presented for the synthesis of pemafibrate. With a primary focus on practicality and efficiency, literature and patent protocols were adapted, optimized, and combined to establish a new, straightforward, and efficient six-step synthetic route that starts from easily accessible and cheap substrates toward enantiopure pemafibrate at the multigram scale.
Morlion et al. (Wed,) studied this question.