tailieunhanh - Synthesis of Novel 10-deoxoartemisinins containing halogens

The synthesis of 10 -allyldeoxoartemisinin (7) in excellent yield through the intermediate, dihydroartemisinin10-benzoate (6) using zinc chloride as a catalyst was performed. This compound was then oxidized by osmium tetraoxide and ozone to give 10 -(2’- carboxymethyl)deoxoartemisinin (8) in good yield. Esterification reaction of this compound with different benzyl alcohols in the presence of EDC and DMAP afforded a series of novel 10- deoxoartemisinins (9a-d) in high yields. | Journal of Chemistry Vol. 44 2 P. 245 - 248 2006 Synthesis of novel 10-DEOXOARTEMISININS CONTAINING HALOGENS Received 20 May 2004 TRAN KHAC vu NGUyEN VAN VIET AND PHAN DINH CHAU Institute of Chemistry Vietnamese Academy of Science and Technology SUMMARy The synthesis of 10f-allyldeoxoartemisinin 7 in excellent yield through the intermediate dihydroartemisinin10a-benzoate 6 using zinc chloride as a catalyst was performed. This compound was then oxidized by osmium tetraoxide and ozone to give 0ft- 2 -carboxymethyl deoxoartemisinin 8 in good yield. Esterification reaction of this compound with different benzyl alcohols in the presence of EDC and DMAP afforded a series of novel 10-deoxoartemisinins 9a-d in high yields. I - INTRODUCTION Malaria one of the world s deadliest diseases is now becoming an increasingly serious problem since malaria parasites develop resistance to drugs such as chloroquine 1 and mefloquine 2 . Therefore the development of new classes of antimalarials is very urgent 1 2 . Artemisinin 3 a sesquiterpene lactone endoperoxide 3 have been used clinically for the treatment of multidrug-resistant Plasmodium falciparum. However the clinical application of artemisinin has been limited by the drug s pharmacokinetic properties. To solve this shortcoming a series of artemisinin derivatives was synthesized such as artemether 5a arteether 5b and artesunate 5c . Analogues of this acetal type are currently being developed as potent and rapidly acting malarials. For more than a decade of using these derivatives in malaria treatment shortcomings like poor bioavailability and rapid clearance are observed principally as a result of the poor chemical and metabolic instability of the acetal function present in these derivatives. This is mainly due to oxidative dealkylation to the intermediate dihydroartemisinin 4 a compound associated with toxicity and short half-life 4 5 . Aspects regarding the chemistry mechanism of action metabolism and toxicity of the .

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• Novel 10 deoxoartemisinins
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