Artemisinin from Artemisia annua

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. 

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. 

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

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. 

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. 

Hao JY, Han W, Huang SD, Xue BY, Deng X. (2002) Microwave-assisted extraction of artemisinin from Artemisia annua L. Sep Purif Technol 28 191-196. 

Currently, artemisinin (18)-based antimalarial therapies remain too expensive to be afforded by those in the developing countries who need them most, due to low yields from the plant of origin, Artemisia annua L., and also due to the high cost of the specialized processing involved in the purification of this compound. In order to solve this problem,... 

Quinghaosu (Artemisinine) Quinghaosu, octahydro-3,6,9-trimethyl-3,12-epoxy-127/-pyrano-(4,3-di)-l,2-benzodioxepin-10-(37/)-one (37.1.1.57), is isolated from the plant Artemisia annua [26]. 

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. 

In 1972, Chinese researchers isolated, by extraction at low temperature from a plant, a crystalline compound that they named qinghaosu [the name artemisinin (la) is preferred by Chemical Abstracts, RN 63968-64-9]. The plant source of artemisinin is a herb, Artemisia annua (Sweet wormwood), and the fact that artemisinin is a stable, easily crystallizable compound renders the extraction and purification processes reasonably straightforward. The key pharmacophore of this natural product is the 1,2,4-trioxane unit (2) and, in particular, the endoperoxide bridge. Reduction of the peroxide bridge to an ether provides an analogue, deoxyartemisinin 3, that is devoid of antimalarial activity. ... 

Artemisinin 9a has been extracted from Artemisia annua L. by supercritical fluid extraction and analyzed by supercritical fluid chromatography (SFC) using a capillary column coupled with a flame ionization detector <1997JCFI(A)353>. The SFC method has also been used for the determination of artemisinin in whole blood <1995JCH(B)183>. 

Nature has been a potential source of therapeutic agents for thousands of years. An impressive number of modem dmgs have been derived from natural sources. Over the last century, a number of top selling dmgs have been developed from natural products. Anticancer dmg vincristine from Vinca rosea, narcotic analgesic morphine from Papaver somniferum, antimalarial dmg artemisinin from Artemisia annua, anticancer dmg Taxol from Taxus brevifolia and antibiotic peniciUins from Penicillium ssp. are just a few examples. 

Artemisia annua and (—)-o -bisabolol from Matricaria recutita (German chamomile). Addition of IPP to GPP produces 2 , 6 -famesylpyropho-sphate (FPP), the precursor for all sesquiterpenes. Farnesylpyrophosphate can cyclize by various cyclase enzymes in various ways, leading to the production of a variety of sesquiterpenes. Some of these sesquiterpenes are medicinally important hioactive compounds. For example, (—)-o -bisabolol and its derivatives have potent anti-inflammatory and spasmolytic properties, and artemisinin is an antimalarial drug. 

Artemisinin 1, a naturally occurring sesquiterpene peroxy-lactone, has been isolated in up to 0.25% yield from the dry leaves of Artemisia annua L.1 Interest in artemisinin is based on its phytomedicinal properties. In 168 b.c. China, as described in a Treatment of 52 Sicknesses, the leaves of A. annua (Qinghao) were used for the treatment of chills and fever.2 It was not until 1972 that the active antimalarial agent qinghaosu was isolated in pure form. This allowed for the unequivocal elucidation of its structure through the use of x-ray crystallography. This complex tetracyclic peroxide is now referred to as artemisinin in various sources such as Chemical Abstracts or the Merck Index. 

Ziffer H, Highet RJ and Klayman DL (1997) Artemisinin an endoperoxidic antimalarial from Artemisia annua L. Prog Chem Org Nat Prod 72, 121-214. 

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