STEROIDAL GEMINAL DIHYDROPEROXIDES AND 1,2,4,5-TETRAOXANES - STRUCTURE DETERMINATION AND THEIR ANTIMALARIAL ACTIVITY

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesiz ed starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyze d addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechani cs calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 b eta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) a nd Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest ac tivity toward D6 clone with IC50 = 155 nM. (C) 1996 by Elsevier Scienc e Inc.