First total synthesis of 3a-hydroxy-1,1-dimethyl-5-((N-methylsulfamoyl)methyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-1-ium 2,2,2-trifluoroacetate by mimicking the oxidative degradation pathway of sumatriptan

Abstract

The expiry date of any medicine is decided based on the time span during which the drug product maintains its quality and is safe as well as effective. The levels of various impurities present in any drug product are considered safe based on various toxicological studies in preclinical species and safety parameters monitoring during clinical studies. The shelf life of US FDA approved sumatriptan auto-injector product ZEMBRACE SymTouch was extended till 36 months after toxicological qualification of the degradation compound 3a-hydroxy-1,1-dimethyl-5-((N-methylsulfamoyl)methyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indol-1-ium 2,2,2-trifluoroacetate. The first total synthesis of this degradation product by mimicking the oxidative degradation pathway of sumatriptan is described herein. © 2021 Elsevier Science. All rights reserved.

Keywords

• Sumatriptan
• Zembrace
• Degradation
• Oxidative cyclization