Yingzhaosu A analogues: synthesis by the ozonolysis of unsaturated hydroperoxides, structural analysis and determination of anti-malarial activity

Ozone-mediated cyclization of a series of unsaturated hydroperoxides 7, pre pared from dienes 2, afforded the corresponding yingzhaosu A analogues 9 in moderate to high yield. X-Ray crystallographic analysis of two yingzhaosu A analogues, endo-9f and 13, showed that the 2,3-dioxabicyclo[3,3,1]nonane system adopts a chair-boat arrangement. Subsequent treatment of endoperoxid es 9 with Ag2O/MeI afforded the expected methyldioxy-substituted cyclic per oxides 14, several of which showed notable anti-malarial activity against P . falciparum in vitro. (C) 2001 Elsevier Science Ltd. All rights reserved.