Artemisinin An AntiMalaria Essay Research Paper INTRODUCTIONThe free essay sample

Artemisinin An Anti-Malaria Essay, Research Paper Introduction The figure people affected by malaria is increasing tremendously. This increasing is due to the fresh drug immune discrepancies of the parasite that causes malaria the Plasmodium. This opposition is a effect of the monolithic usage of the quinoline-related drugs over the last decennaries. In this scenario, it became of import to seek for new drugs, active against fresh biochemical parasite marks. The drug known as artemisin or Qinghaosu ( 1 ) , is a consequence of Chinese authorities run, to seek for new active drugs against malaria, in Chinese medicative workss. In the general mechanism accepted for the action of artemisin, the free heme group, obtained during the haemoglobin digestion is proposed to catalyze the formation of oxyl groups, by oxidization of the Fe ( II ) to Fe ( III ) and the decrease of the endoperoxide bond. These oxyl groups rearrange in to C-centred groups that are cytotoxic to the parasite by alkylation of critical parasite proteins. In the experiments directed in Liverpool, the first measure was to seek to synthesize fresh artemisin derived functions and so to make a biomimetic survey, with these compounds and the Fe salt FeCl. In the first experiment carried, it was tried to synthesize an quintessence ( 2 ) of the dihydroartemisin ( 3 ) and tetrazol chloride ( 4 ) , utilizing a method developed by University of Algarve Organic Chemistry group ( see scheme 1 ) Scheme 1 In the undermentioned experiments, and utilizing a different methodological analysis, it was tried to synthesize, with artemisin benzoate ( 5 ) and p-trifluoromethoxi phenol ( 6 ) as get downing stuff, the trifluoromethoxi phenol substituted compound ( 7 ) ( see scheme 2 ) Scheme 2 At last, it was done a biomimetic survey, responding the obtained compound with the Fe salt FeCl ( scheme 3 ) , arising two different merchandises: the one resulting from the formation of a primary C centred extremist ( 8 ) ; and from the formation of a secondary C-centered group ( 9 ) . Scheme 3 EXPERIMENTAL SECTION AND RESULTS Experiment I: Synthesis of Compound 2 The tetrazole chloride ( 0,12 g, 0,67 mmol ) was added to a solution of dihydroartemisin and NaH ( 0,053 mmol ) in dried tetrahydrofuran. The solution was stirred for 1 hr. The T.L.C. show that after this clip, there wasn T any merchandise on the reaction pot and the reaction should remain longer stirring Experiment II: Synthesis of Compound 7 A solution of benzoate ( 0.409, 1mmol ) in anhydrous dychlorometane ( 5 milliliter ) was added to a mixture of p-trifluoromethyl phenol ( 0.811, 5 mmol ) and ZnCl2 ( 0.1759, 1.25 mmol ) in anhydrous dychloromethane ( 4 milliliter ) , at 0| C.. The reaction was stirred for 1 hr and 15 proceedingss and followed by T.L.C. utilizing as eluent a solution of 75 % hexane, 25 % ethyl ethanoate. The reaction was so, diluted with ethyl ethanoate and washed 3 Ti Maines with a solution of 5 % of citric acid, saturated aqueous solution of Sodium hydrogencarbonate and dried with Mg sulfate. The dissolver was evaporated to dryness and the coveted merchandise was isolated utilizing a silicon oxide gel flash chromatography column ( with the same eluent used on the T.L.C. ) , recristalized, and was done an N.M.R. spectrometry. The output of this reaction was 19,7 % . Experiment III: Synthesis of Compound 7 The former process was repeated as antecedently described but in this experiment, the reaction was stirred at 0|C. for 2 hours, and left stirring during the dark at room temperature. The eluent used in the T.L.C. and in the silicon oxide flash chromatography column was besides changed. It was used a solution of 85 % of methylbenzene, 15 % of dychloromethane. In this instance there wasn T a great improve in the output ( 33.3 % ) , so the following measure will be to utilize a greater sum of the Lewis acid. Experiment IV: Synthesis of Compound 7 The former process was repeated as antecedently described but in this experiment, it was used 5mmol of the Lewis acid ( ZnCl2 ) and the reaction was stopped after two hours. The eluent used in the T.L.C. and in the silicon oxide flash chromatography column was besides changed. It was used a solution of 75 % of dychloromethane and 25 % of hexane. In the present experiment, the output was 67,7 % . Experiment V: Isomerization of the compound 7 The FeCl ( 68 milligram, 0,33 mmol ) was added to a solution of the compound III ( 150 milligram, 0,34 mmol ) in acetonitrile and was stirred for 45 proceedingss. The reaction was followed by T.L.C. utilizing 60 % methylbenzene, 40 % dychloromethane as eluent. The solution was filtered with celite, washed with dychloromethane and ethyl ethanoate and evaporated until waterlessness. The oil collected was purified utilizing a silicon oxide gel flash chromatography column with the same eluent. Merely a little sum of merchandise was isolated since it seemed like the merchandises interact with the silicon oxide gel. Experiment Six: The former experiment was repeated, but to insulate the merchandise, since it was suspected that the resulting merchandises somehow interact with the silicon oxide gel a impersonal aluminum oxide column was used with a solution of 80 % crude oil quintessence, 20 % ethyl ethanoate as eluent. At list one of the merchandises was isolated but the output was non determined. Recognitions I wish to thank to: Professora Lurdes and Professor Amadeu, non merely for the part that made this great chance happen, but besides for all forbearance, aid and knowledge given me during the last twelvemonth. Dr. Storr and Dr. Paul O Neill whose kindness, understanding, comprehension and support, made this dream possible. Rui, Ricardo, Steve, Vick, Tatiana and Ollie for all the aid and friendly relationship. I besides would wish to thank to the University of Liverpool for leting me to utilize all the installations.