A CARBONYL OXIDE ROUTE TO ANTIMALARIAL YINGZHAOSU-A ANALOGS - SYNTHESIS AND ANTIMALARIAL ACTIVITY

Ozonolysis of R-carvone and in situ trapping with primary alcohols ROH (R = Me, Et, Bu, Pent, Oct) produces hydroperoxy ketals (5a-e) as a 1 :1 mixture of diastereomers. Cyclisation of these intermediates with c atalytic sodium methoxide in methanol produces the corresponding endop eroxide derivatives (6a-6e). The pentyl and octyl endoperoxide derivat ives demonstrate reasonable antimalarial potency in vitro against the HB3 strain of Plasmodium falciparum. A mechanism for antimalarial acti on involving the formation of a C-centred radical is proposed. (C) 199 8 Published by Elsevier Science Ltd. All rights reserved.