Synthesis of novel artesunate-benzothiophene and artemisinin-benzothiophene derivatives

Ozok O., Kavak E., Kıvrak A.

NATURAL PRODUCT RESEARCH, vol.36, no.20, pp.5228-5234, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36 Issue: 20
  • Publication Date: 2022
  • Doi Number: 10.1080/14786419.2021.1928116
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, CINAHL, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.5228-5234
  • Keywords: Artemisinin, artesunate, benzothiophene, drug design, natural products, wormwood plant
  • Van Yüzüncü Yıl University Affiliated: Yes


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.