[Extraction of artemisinin and synthesis of its derivates artesunate and artemether].
Artemisinin is extracted from Artemisia annua, a shrub also known as sweet wormwood that was used in traditional medicine in Asia for more than 1500 years. Recent studies in numerous malarious zones have demonstrated the effectiveness of artemisinin and have reported no evidence of the resistance now associated with almost all other antimalarials on the market. Despite its remarkable activity, artermisinin is not accessible to many patients due to high cost. This situation confronts all players in the fight against malaria with the urgent need to develop a simple process to produce massive supplies of artemisinin and its derivative at an affordable price. The purpose of the study described here was to develop a simple, cost-effective method that could be used by all professionals to extract artemisinin and transform it into artesunate or artemether. Artemisinin was extracted with dichloromethane and purified on the basis of variations in polarity and in the hydrophile/lipophile balance of solvents. Transformation into artesunate was a two-step process involving reduction to dihydroartemisinin using diisobutylaluminium hydride (DIBAL) followed by esterification using succinic anhydride. Artemether was obtained from dihydroartemisinin using boron trifluoride. Extraction using dichloromethane presents several advantages. Since dichloromethane is not explosive it can be safely transported and used for extraction on farms where Artemisia annua is grown. Evaporation and recovery of dichloromethane is relatively easy so that it can be re-used. These advantages result in a significant decrease in purchasing and shipping costs. Extraction on the farm eliminates the expense and facilities that would otherwise be required to transport and store leaves at the laboratory (250 kg of leaves yield 4 to 5 kg of raw artemisinin extract that yields approximately 1 kg of pure artemisinin). The low-cost process described here is feasible for any pharmaceutical laboratory including those in developing countries.
Chekem
L
L
Laboratoire de recherches pharmaceutiques, Propharex SA, Courcelles, Belgique. l.chekem@propharex.com
Wierucki
S
S
D000077549:Artemether; D037621:Artemisinins / Q000138:chemical synthesis* / Q000302:isolation & purification*; D000077332:Artesunate; D002626:Chemistry, Pharmaceutical / Q000379:methods; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000302:isolation & purification*
D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C031327:artemisinin; D000077549:Artemether