Water-soluble qinghaosu derivatives

Sodium artesunate is the first water-soluble qinghaosu derivative and used for treatment of the severe malaria patients by intravenous or intramuscular administration. However, the aqueous solution is unstable, and its hydrolysis product,... 

In view of the known basic antimalarial drugs (such as chloroquine, quinine) that are being used as salts for injection, it was proposed that introducing an amino group into the qinghaosu molecule may lead to water-soluble derivatives. Thus, five types of basic qinghaosu derivatives were synthesized (Structure... 

Accordingly, as the first step, the interaction of qinghaosu and cysteine in the presence of a catalytic amount of Fe(lFlll) was studied. From the reaction mixture, a water-soluble compound was isolated. This compound could be visualized with ninhydrin on TLC, and it showed a formula of C16H27NO6S H2O. Treatment of this compound with acetic anhydride yielded a cyclic thioether 165, which in turn undoubtedly showed the formation of adduct 166 of 1 and cysteine through a a bond between C-3 and sulfur. A stable adduct 167 of cysteine and 170 was then isolated in 33% yield with the same reaction protocol. As mentioned, both adducts of cysteine with primary and secondary free radical derived from arte-mether were also identified recently, albeit in low yield (Structure 5-25). More... 

When dihydroartemisinin was found to be more active than qinghaosu and the introduction of the hydroxy group into the molecular nucleus could not improve its solubility in water, three types of dihydroartemisinin derivatives were synthesized and evaluated in China (Scheme... 

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