Antimalarial peroxide dyads from natural artemisinin and hydroxyalkylated 1,2,4-trioxanes.
Three synthetic approaches to highly antimalarial peroxide dyads that are composed of the natural artemisinin part (either as dihydroartemisinin or artesunic acid components) and synthetic 1,2,4-trioxanes linked by ether or ester bridges are described. Photooxygenation is the key step to introduce the trioxane group initially or at the end of the reaction sequence, respectively. Dihydroartemisinin or artesunate coupling to hydroxyethyltrioxanes are the two processes that use intact peroxide units from the beginning, whereas the dihydroartemisinin-coupling to an allylic alcohol is a postphotooxygenation route, where the second trioxane ring is installed in the last step of the procedure.
Griesbeck
Axel G
AG
Department of Chemstry, Organic Chemistry, University of Cologne, Greinstrasse 4, 50939 Köln, Germany. griesbeck@uni-koeln.de
Neudörfl
Jörg
J
Hörauf
Achim
A
Specht
Sabine
S
Raabe
Angela
A
D000962:Antimalarials / Q000138:chemical synthesis*; D037621:Artemisinins / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D010545:Peroxides / Q000138:chemical synthesis*; D055668:Photochemical Processes; D012717:Sesquiterpenes / Q000737:chemistry
D000962:Antimalarials; D037621:Artemisinins; D004987:Ethers; D006573:Heterocyclic Compounds, 1-Ring; D010545:Peroxides; D012717:Sesquiterpenes; D010100:Oxygen