Synthesis of novel artesunate-benzothiophene and artemisinin-benzothiophene derivatives

Abstract

Natural products are used for the treatment of a variety of diseases for many years. Last decades, design and synthesis of novel biologically active hybrid molecules including natural product is gained big importance due to their unique and new biological properties. In the present study, novel artemisinin-benzothiophene derivatives (12 A-F) are synthesised. Initially, benzothiophene derivatives (4 A-4F) are prepared via the Pd-catalyzed coupling reactions and iodocyclisation reactions. Then, Suzuki-Miyaura coupling reactions were used for the formation of intermediates 6 A-6F (between 64% and 91% yields). Finally, the Steglich esterification reaction between intermediate 6 and artesunate formed the artemisinin-benzothiophene hybrids (9 A-9F) in moderate to excellent yields under very mild reaction conditions. When intermediate 6 was reacted with dihydroartemisinin, product 12 A-12F was also obtained with high yields.

Keywords:

• Artemisinin
• artesunate
• benzothiophene
• natural products
• drug design
• wormwood plant

Acknowledgment

The authors thank to The Scientific and Technological Research Council of Turkey (TUBITAK) project 218Z028 for chemicals and solvents. O. Ozok thanks to the council of higher education (YOK) for 100/2000 scholarships. In addition, E. Kavak and O. Ozok thank to TUBITAK STAR scholarships.The author (A. Kivrak) would like to acknowledge networking contribution by the COST Action CA17104 ‘New diagnostic and therapeutic tools against multidrug resistant tumours’.

Disclosure statement

No potential conflict of interest was reported by the authors.