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Diastereoselective Synthesis of β‐Ether Derivatives of Artemisinin, an Antimalarial Drug: The Effect of Nitrile on Stereoselectivity
Author(s) -
Chand Hemender R.,
Bhattacharya Asish K.
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201500415
Subject(s) - artemisinin , chemistry , artemisia annua , dihydroartemisinin , stereoselectivity , nitrile , artemether , yield (engineering) , ether , population , dichloromethane , organic chemistry , malaria , combinatorial chemistry , plasmodium falciparum , catalysis , materials science , demography , solvent , sociology , metallurgy , immunology , biology
Malaria is a life‐threatening disease affecting a major portion of the world's population with considerable loss of human life. Artemisinin, isolated from Artemisia annua , its oil‐ and water‐soluble derivatives, and other known antimalarials are recommended for artemisinin combination therapy by the World Health Organization. We have established a method for the stereoselective synthesis of β‐ether derivatives of dihydroartemisinin in high yield and high diastereoselectivity. The reaction either in acetonitrile or dichloromethane/trichloroacetonitrile (6:1) mixtures at 0 °C or room temperature, respectively, furnished the antimalarial drugs artemether 3 or arteether 4 in high yield with a high diastereomeric ratio. The effect the nitrile has on the yield and stereoselectivity is mechanistically explained.