Artemisinic acid, artemisinin synthesis

The entire biosynthesis pathway of artemisinin has not been elucidated yet. The first committed step is conversion of FPP to amorphadiene via the cyclization catalyzed by ADS [102] followed by further oxidations of amorphadiene to artemisinic acid. Artemisinic acid can be used as a precursor for semi-synthesis of artemisinin and related chemicals [88]. 

Using various derivatives of artemisinic acid, the methodology onthned in Scheme 184 was extended to the synthesis of a nnmber of modified artemisinin-type tetracychc trioxanes. For example, the syntheses of 6,9-desdimethylartemisinin 586a , A-fi-hydroxyartemisinin , and C9-alkylated artemisinin analognes were reported . In some cases it is possible to avoid the lactonization step while preserving the ester fnnctionality and interrnpting the cychzation of aldehyde-peroxyhemiacetals of type 652, at the step of formation of tricyclic 5-hydroxy-1,2,4-trioxane . ... 

The biosynthesis of artemisinin3 is of interest in that it provides clues to the chemical synthesis of artemisinin from its more abundant precursor in A. annua, artemisinic acid 2. Conjugate reduction of the acrylate double bond of 2 followed by singlet oxygenation leads,... 

Scheme 22.6 Synthesis of the antimaiariai artemisinin from artemisinic acid.

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