Artemisinic artemisinin

Quinghaosu is the latest fundamental discovery in this area and is a heterocyclic compound that does not have a nitrogen atom in its structure. It is taken from a Chinese folk medicine. It is isolated from the plmt Artemisia annua. It is amazing that this compound, which is completely different than the other drugs described in this chapter in terms of structure, exhibits the exact same therapeutic effect. The main interest in quinoghaosu is based on the fact that it is active against resistant forms of malaria caused by P falciparum, and even its cerebral forms. Synonyms of this drug are artemisine, artemisinin, and others. 

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]. 

Scheme 8. Summary of the biosynthetic pathway to artemisinin through artemisinic alcohol in Artemisia annua.

Artemisinic acid can indeed be easily converted to artimisinin using conventional chemistry in three steps via reduction of the exocyclic methylene group and photooxidation of the resulting dihydroartemisinic acid, with 30% overall yield (see Scheme 9) Other artemisinin derivatives have also been prepared using artemisinic acid as the starting material. ... 

Roth RJ, Acton N. (1989) A simple conversion of artemisinic acid into artemisinin. J Nat Prod 52 1183-1185. 

Haynes RK, Vonwiller SC. (1994) Extraction of artemisinin and artemisinic acid Preparation of artemether and new analognes. Trans R Soc Trap Med Hyg 88 23-26. 

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,... 

Vroman, J.A., Khan, I., and Avery, M.A. Copper (I) catalyzed conjugate addition of Grignard reagents to acrylic acids homologation of artemisinic acid and subsequent conversion to 9-substituted artemisinin analogs, Tetrahedron Lett., 38, 6173, 1997. 

In conclusion, the vast literature and its derivatives, particularly artesunate, artemether, and arteether, point out to the need to make these derivatives in quantities that would reduce their current production cost to make these drugs accessible to the economically underprivileged societies that are often the victims of malaria. A recent promising method in which artemisinic acid, a precursor to artemisinin, has been produced in engineered yeast. Therefore, microbially produced artemisinic acid holds promise to the syntheses of antimalarial drugs at affordable prices <2006N940>. Furthermore, anticancer activities of artemisinin 1 and its derivatives have been reviewed <2005MI995>. 

Haynes, R. K. Vonwiller, S. C. Catalysed oxygenation of allyhc hydroperoxides derived from Qinghao (artemisinic) acid. Conversion of qinghao acid into dehydroqinghaosu (artemisitene) and qinghaosu (artemisinin). J. Chem. Soc. Chem. Commun., 1990, 451 53. 

---