1.
Bioorg Med Chem Lett
; 16(11): 2991-5, 2006 Jun 01.
Article
in English
| MEDLINE
| ID: mdl-16527481
ABSTRACT
A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides.
Subject(s)
Alkanes/chemistry , Alkanes/pharmacology , Alkenes/chemistry , Alkenes/pharmacology , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Oxygen/chemistry , Sulfhydryl Compounds/chemistry , Alkanes/chemical synthesis , Alkenes/chemical synthesis , Animals , Antimalarials/chemistry , Cyclization , Cyclohexenes , Epoxy Compounds/chemistry , Limonene , Molecular Structure , Peroxides/chemistry , Plasmodium berghei/drug effects , Structure-Activity Relationship , Terpenes/chemistry
2.
Angew Chem Int Ed Engl
; 43(32): 4193-7, 2004 Aug 13.
Article
in English
| MEDLINE
| ID: mdl-15307085