Synthesis and characterization of potential stereoisomeric and degradation impurities of ulipristal acetate

Abstract

Ulipristal acetate (UPA) was developed by Laboratoire HRA Pharma, France and approved by the FDA for emergency contraception in August 2010. Though several methods have been developed for the synthesis of UPA, the steroidal impurities would appear inevitably and have not been reported in detail. In this work, several stereoisomeric and N,N-didemethylated impurities of UPA were analyzed and synthesized. The stereoisomers were obtained through an efficient and practical approach, and the structure of the key stereoisomer U-1 was confirmed by single-crystal X-ray analysis. Our research would be important and valuable for the quality control of UPA manufacturing.