Synthesis and separation of methyl-4-(p-substituted phenyl)-4-(R or S)((10-alpha or 10-beta)-dihydroartemisininoxy)butyrate

Artemisinin (1) is used as an antimalarial drug but its effectiveness is impaired by: (1) Its high rate of recrudescence (malaria relapses); (2) Poor solubility in both water and oil; (3) Short plasma half-life; (4) Poor oral activity (active only in very high dosage); (5) Severe CNS toxicity. This work describes an effort to obtain more effective antimalarial analogs by synthesizing methyl-4-(p-substituted phenyl)-4-(R or S) ((10$\alpha$ or 10$\beta$)dihydroartemisininoxy) butyrate.