6533b82efe1ef96bd129333b

RESEARCH PRODUCT

Total Synthesis and Biological Investigation of (−)‐Artemisinin: The Antimalarial Activity of Artemisinin Is not Stereospecific

Ean-jeong SeoThomas A. EfferthToni SmeilusAthanassios GiannisMarcel KaiserMarcel KaiserJohannes Krieger

subject

ArtemisininsCell SurvivalPlasmodium falciparum010402 general chemistry01 natural sciencesCatalysisAntimalarialsStereospecificityCell Line Tumorparasitic diseasesmedicineHumansArtemisininbiology010405 organic chemistryChemistryTotal synthesisStereoisomerismPlasmodium falciparumGeneral Chemistrybiology.organism_classificationCombinatorial chemistryArtemisinins0104 chemical sciencesCyclizationDrug Resistance NeoplasmMonoterpenesmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2018-07-02Angewandte Chemie International Edition
https://doi.org/10.1002/anie.201802015