Artemisia annua

In the example below, Bhardwaj and coworkers synthesized tetramethoxyflavone 36 this flavonol was believed to be the structure of a compound isolated from Artemisia annua Methyl ketone 37 and aldehyde 38 were smoothly condensed to afford chalcone 39 in 73% yield. 39 was then converted to 40 under slightly modified AFO conditions in low yield. Selective demethylation of 40 gave 36. However, spectral data and melting point data of 36 did not match up with the compound isolated from the plant. Hence, the original structure was misassigned and was not flavonol 36. 

Mercke, P., Bengtsson, M., Bouwmeester, H.J. etal. (2000) Molecular cloning, expression, and characterization of amorpha-4,11 -diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Archives of Biochemistry and Biophysics, 381, 173-180. 

Duke MV, Paul RN, Elsohly HN, Sturtz G, Duke SO (1994) Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. Int J Plant Sci 155 365-372... 

How do traditional remedies fare in such trials Some perform quite well and prove to be highly effective, but others are no better than placebos. One striking success is an extract of sweet wormwood (Artemisia annua), which Chinese physicians have prescribed for the chills and fevers of malaria for more than two thousand years. About twenty-five years ago, Chinese chemists obtained from sweet wormwood its principal active component, a compound now called artemisinin. Clinical trials on malaria patients in Southeast Asia agreed with Chinese tradition on the value of artemisinin and also identified a few even more useful drugs prepared from it in the laboratory. These compounds are effective against the deadliest form of malaria and are now frequently the therapies of choice for treating it. 

Ziffer H, Highet RJ, Klayman DL. (1997) An endoperoxidic antimalarial from Artemisia Annua L. In Herz W, Kirby GW, Moore RE, Steglich W. (eds). Progress in the Chemistry of Organic Natural Products, pp. 121-202, Spinger-Verlag, Wien. 

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

Chang YJ, Song SH, Park SH, Kim SU. (2000) Amorpha-4,11-diene synthase of Artemisia annua cDNA Isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis. Arch Biochem Biophys 3S3 178-184. 

Schramek N, Wang HH, Romisch-Margl W, Keil B, Radykewicz T, Winzenhorlein B, Beerhues L, Bacher A, Rohdich F, Gershenzon J, Liu BY, Eisenreich W. (2010) Artemisinin biosynthesis in growing plants of Artemisia annua. A (C02)-C-13 study. Phytochemistry 71 179-187. 

Teoh KH, Polichuk DR, Reed DW, Nowak G Covello PS. (2006) Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. FEBS Lett 580 1411-1416. 

Bertea CM, Freije JR, van der Wonde H, Verstappen FW, Perk L, Marquez V, De Kraker JW, Posthumus MA, Jansen BJ, de Groot A, Franssen MC, Bouwmeester HJ. (2005) Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. Planta Med 71 40 7. 

Weathers PJ, Elkholy S, Wobbe KK. (2006) Artemisinin the biosynthetic pathway and its regnlation in Artemisia annua, a terpenoid-rich species. In Vitro Cell Developmental Biol — Plant 42 309-317. 

Wang JW, Tan RX. (2002) Artemisinin production in Artemisia annua hair root cultures with improved growth by altering the nitrogen source in the medium. Biotechnol Lett 24 1153-1156. 

Artemisinin, a tetracyclic 1,2,4-trioxane isolated from Artemisia annua L., is currently recommended as a first-line agent against Plasmodium falciparum malaria. Artemisinin and its synthetic derivatives have also been shown to be promising prototypes for the development of new antiproliferative agents. This chapter presents the recent advances on the analytic methods for extraction and quantification of artemisinin from A. annua plants as well as the biological properties of this natural product. 

Artemisia ketone (2) Artemisinic alcohol (3) Arteannuin B (4) 1,8-Cineole (5) Camphor (6) Fig. 2. Examples of some secondary metabolites isolated from Artemisia annua. 

Analytic Methods for Artemisinin Extraction and Quantification from Artemisia annua... 

Malik AA, Ahmada J, Mir SR, Ali M, Abdin MZ. (2009) Influence of chemical and biological treatments on volatile oil composition of Artemisia annua Linn. Ind Crops Prod 30 380-383. 

Ridder S, Kooy FV, Verpoorte R. (2008) Artemisia annua as a self-reliant treatment for malaria in developing countries. J Ethnopharmacol 120 302-314. 

Dias PC, Foglio MA, Possenti A, Nogueira DC, de Carvalho JE. (2001) Antiulcerogenic activity of crude ethanol extract and some fractions obtained from aerial parts of Artemisia annua L. Phytother Res 15 670-675. 

Foglio MA, Dias PC, Antonio MA, Possenti A, Rodrigues RA, da Silva EF, Rehder VL, de Carvalho JE. (2002) Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua. Planta Med 68 515-518. 

Romero MR, Serrano MA, Vallejo M, Efferth T, Alvarez M, Marin JJ. (2006) Antiviral effect of artemisinin from Artemisia annua against a model member of the Flaviviridae family, the bovine viral diarrhoea virus (BVDV). Planta Med 72 1169-1174. 

Liu CZ, Zhou HY, Zhao Y. (2007) An effective method for fast determination of artemisinin in Artemisia annua L. by high performance liquid chromatography with evaporative light scattering detection. Anal Chim Acta 581 298-302. 

Artemisia annua L. by reversed phase HPLC. J Liq Chromatogr Relat Tech 28 705-712. 

Elsohly HN, Croom EM, Elsohly MA. (1987) Analysis of the antimalarial sesquiterpene artemisinin in Artemisia annua by high-perfomance liquid chromatography (HPLC) with postcolumm derivation and ultraviolet detection. Pharm Res 4 258-260. 

Rodrigues RAF, Foglio MA, Junior SB, Santos AS, Rehder VLG. (2006) Optimization of the extraction and isolation of the antimalarial drug artemisinin from Artemisia annua L. Quim Nova 29 368-372. 

Quispe-Condori S, Sanchez D, Foglio MA, Rosa PTV, Zetzl C, Brunner G Meireles MAA. (2005) Global yield isotherms and kinetic of artemisinin extraction from Artemisia annua L leaves using supercritical carbon dioxide. J Supercriti Fluids 36 40 8. 

Tzeng TC, Lin YL, Jong TT, Chang CMJ. (2007) Ethanol modified supercritical fluids extraction of scopoletin and artemisinin from Artemisia annua L. Separ PurifTech 56 18-24. 

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