Synthesis of amide bridged artesunate benzothiophene derivatives

The artemisinin molecule, a natural product, was discovered by Dr. Tu YouYou in 1970 and is still the most effective malaria drug used today. Recently, not only the treatment of malaria but also various treatments such as cancer have been used. It has been revealed that artemisinin is also effective along with artemisinin. Literature studies show that the majority of them focus on the new biological effects of artemisinin and its semi-synthetic derivatives such as artemether, dihydroartemisinin, and artesunate. In this study, different derivatives were synthesized by combining the artemisinin molecule with a benzothiophene-amide bridge. Benzothiophene and its derivatives exhibit anti-inflammatory, anti-cancer, anti-fungal, and anti-depressant biological properties. It is known that derivatives containing a heteroaromatic group such as benzothiophene increase the biological activity. In our study, new artemisinin-benzothiophene derivatives with an amide bridge were designed using the artemisinin molecule isolated from the Pelin plant, a natural product, and benzothiophene, and their synthesis and characterization were carried out. First, using the developed methods (electrophilic cyclization reaction, Sonogashira coupling reaction, Steglich esterification reaction, and Suzuki-Miyaura coupling reaction), 9 derivatives containing amide-bridged artesunate-benzothiophene were synthesized with quite good yields. The molecular elucidation of the synthesized final products was identified by spectroscopic methods.