Modification on C-12 of Qinghaosu

From the view of chemistry, the C-12 position of dihydroartemisin is similar to the C-1 position of carbohydrates. So, these C-12 derivatives may be divided into three types 0-glycosides, A-glycosides, and C-glycosides using a similar term in carbohydrate chemistry. 

The ethers and esters of dihydroartemisinin noted above may be considered as its (9-glycosides (126) (Structure 5-10). 

Venugopalan et al. also prepared some ethers and thioethers of dihydroartemisinin.Haynes et al. synthesized many new C-12 esters and ethers of dihydro- artemisinin. Compared with similar work performed 20 years ago, they successfully prepared some (3-aromatic esters of dihydroartemisinin by means of Schmit and Mitsunobu procedures. 

Another type of (9-glycosides (127), 12-(3 aryl ethers of dihydroartemisinin, was synthesized by a reaction of acetyl dihydroartemisinin or trifluoroacetyl dihydroartemisinin with various substituted phenols in the presence of trifluoroacetic acid. Most of these compounds were proved to have better antimalarial activity against P. berghei in mice than qinghaosu, but less activity than artemether. Unexpectedly, 

R = CH2CH=CH2, CH=CH2, CH2CH2CHO CH2CHO, CH2COR, CH2CH(0H)R, CH2CH(0H)CF3, CH2COPh, CN, 

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