Synthesis and Structural Diversification of Artemisinins towards the Generation of Potent Anti-malarial Agents

Artemisinin and its semi-synthetic derivatives have been the cornerstone of malaria chemotherapy. Their life-saving therapeutic effects and characteristic structure bearing a peroxide bridge in a sesquiterpene lactone framework have attracted the attention of both synthetic chemists and synthetic biologists. In this highlighted review, the engineered biosynthesis, chemo-enzymatic synthesis, total synthesis and derivatization via siteselective C-H functionalization are outlined as state-of-the-art approaches for the artificial production of artemisinin and its derivatives. To gain rapid and flexible access to the chemical space relevant to artemisinins, two synthetic campaigns that produce both skeletally diverse tetracyclic peroxides and 6-aza-artemisinins are summarized.

Automated summary

Artemisinin and its semi-synthetic derivatives have been crucial in malaria chemotherapy due to their life-saving effects and unique peroxide bridge structure. This review outlines state-of-the-art approaches for artificial production, including engineered biosynthesis, chemo-enzymatic synthesis, total synthesis, and derivatization via siteselective C-H functionalization. Additionally, two synthetic campaigns producing skeletally diverse tetracyclic peroxides and 6-aza-artemisinins are summarized for rapid and flexible access to artemisinin-related chemical space.