Drug Development of the Antimalarial Agent Artemisinin: Total Synthesis, Analog Synthesis, and Structure-Activity Relationship Studies
Final rept. 15 Oct 1987-14 Oct 1990
SRI INTERNATIONAL MENLO PARK CA
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The enantioselective total synthesis of -artemisinin has been optimized and carried out at multigram scale. An alternate approach to the total synthesis afforded racemic 6, 9-desmethylartemisinin 79 and a related analog 80. A synthetic intermediate from the total synthesis, -acid 32, has been alkylated and led to numerous C-alkylartemisinin analogs 42 - 63. The acid 32 has also been converted into various N-alkyl amides, which in turn finished 11- azaartemisinin analogs 64-69. Selected various alkyted analogs were converted into the corresponding dihydro-, alkylether derivatives 70-78 based on arteether-type antimalarials. The total synthesis involved the substitution of a cyclohexyl ring, but at various stages the elaboration of cyclohexanes with less than the total number of requisite substituents resulted in the synthesis of ring cleaved analogs and partial structures of artemisinin.
- Medicine and Medical Research