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INTRODUCTION The number people affected by malaria is increasing enormously This increasing is due to the novel drug resistant variants of the parasite that causes malaria the Plasmodium This resistance is a consequence of the massive use of the quinoline-related drugs over the last decades In this scenario it became important to search for new drugs active against novel biochemical parasite targets The drug known as artemisin or Qinghaosu 1 is a result of Chinese government campaign to search for new active drugs against malaria in Chinese medicinal plants In the general mechanism accepted for the action of artemisin the free haem group obtained during the haemoglobin digestion is proposed to catalyse the formation of oxyl radicals by oxidation of the FeII to FeIII and the reduction of the endoperoxide bond These oxyl radicals rearrange in to C-centred radicals that are cytotoxic to the parasite by alkylation of vital parasite proteins In the experiments directed in Liverpool the first step was to try to synthesise novel artemisin derivatives and then to do a biomimetic study with these compounds and the iron salt FeCl In the first experiment carried it was tried to synthesise an ether 2 of the dihydroartemisin 3 and tetrazol chloride 4 using a method developed by University of Algarve Organic Chemistry group see scheme 1 Scheme 1 In the following experiments and using a different methodology it was tried to synthesise with artemisin benzoate 5 and p-trifluoromethoxi phenol 6 as starting material the trifluoromethoxi phenol substituted compound 7 see scheme 2 Scheme 2 At last it was done a biomimetic study reacting the obtained compound with the iron salt FeCl scheme 3 originating two different products the one resulting from the formation of a primary carbon centred radical 8 and from the formation of a secondary C-centered radical 9 Scheme 3 EXPERIMENTAL SECTION AND RESULTS Experiment I Synthesis
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