A series of N-substituted 11-azaartemisinins were prepared in high yield em
ploying base-catalyzed additions to an amide nitrogen of olefins and termin
al acetylenes conjugated with electron withdrawing groups (EWGs). When the
terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or
carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were
obtained when the EWG was a nitrile. In vitro antimalarial activities of e
ach compound were determined against two drug-resistant strains of Plasmodi
um falciparum. Many of the compounds prepared were several times more activ
e than artemisinin. (C) 2000 Elsevier Science Ltd. All rights reserved.