OOOOOHHHHArtemisinin 11234565a788a12a9101112
(+) Artemisinin 1, a sesquiterpene endoperoxide lactone with an unprecedented structure is a natural medicine for the treatment of malaria, in particular drug against drug resistant and cerebral malaria. The exceptional pharmacological potential and extreme scarcity of the natural material together with its complex structure prompted us to study the total synthesis of (+) Artemisinin. The architectural complexity is attributed to the presence of 7 chiral centers with tetracyclic framework with an endoperoxide unit. Though many valuable contributions5-9 have been made towards the total synthesis of this unique structurally complex molecule, the need for a simple strategic route still remains, encouraging us to take up the total synthesis of this potent antimalarial drug.
Results and Discussion
In the retrosynthetic analysis (scheme 1), among all the valuable contributions for the total synthesis of Artemisinin, we believe that the key intermediate would be a-hydroperoxy aldehyde which can be easily photo oxygenated from methylvinylether 2 because, in a ketalization-like process, simple cyclodehydration of a-hydroperoxy aldehyde should readily furnish the tetracyclic natural product 1. Thus, the next intermediate in our analysis was the iodolactone 3 which has required stereochemistry and further it can be easily prepared from the starting (+) isolimonene 4 which has two asymmetric carbon atoms having the same absolute configuration as the target molecule.
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Scheme 1
