Design, synthesis, and biological evaluation of a series of simple and novel potential antimalarial compounds

A series of compounds bearing an endocyclic -N-O- moiety with potential ant imalarial activity based on simple derivatives of the tropolone purpurogall in was prepared by means of a hetero Diels-Alder reaction using nitrosobenz ene as a dienophile. The rationale behind the design of these compounds is presented, together with the synthetic route to derivatives bearing aromati c and aliphatic esters of the C4 ' -position hydroxyl group of the purpurog allin framework, as well as biological data obtained from in vitro assays a gainst Plasmodium falciparum and Trypanosoma cruzi. Several of the new comp ounds have activities in the 3-9 muM range, acid provide leads for the deve lopment of a novel class of antiparasitic drugs with improved biological an d pharmacological properties. (C) 2001 Elsevier Science Ltd. All rights res erved.