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Total Synthesis and Biological Investigation of (−)‐Artemisinin: The Antimalarial Activity of Artemisinin Is not Stereospecific
Author(s) -
Krieger Johannes,
Smeilus Toni,
Kaiser Marcel,
Seo EanJeong,
Efferth Thomas,
Giannis Athanassios
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201802015
Subject(s) - artemisinin , plasmodium falciparum , malaria , stereospecificity , biology , chemistry , combinatorial chemistry , biochemistry , immunology , catalysis
Here, we describe an efficient and diversity‐oriented entry to both (−)‐artemisinin ( 1 ) and its natural antipode (+)‐artemisinin, starting from commercially and readily available S ‐(+)‐ and R ‐(−)‐citronellene, respectively. Subsequently, we answered the still open question regarding the specificity of artemisinins action. By using a drug‐sensitive Plasmodium falciparum NF54 strain, we showed that the antimalarial activity of artemisinin is not stereospecific. Our straightforward and biomimetic approach to this natural endoperoxide enables the synthesis of artemisinin derivatives that are not accessible through applying current methods and may help to address the problem of emerging resistance of Plasmodium falciparum towards artemisinin.