RESUMO
Verrucarin A (2) was epoxidized to give the beta-9,10-epoxide 7 (major product) and alpha-9,10-epoxide 9 (minor product). The beta-epoxide 7 and its acetate 8 exhibit high in vivo antileukemic activity against P-388 mouse leukemia, whereas 2 and 9 are inactive. Epoxidation of verrucarin B (3) and roridin A (1) to their respective beta-9,10-epoxides (11 and 12, respectively) also yields compounds with substantially increased activity. Allylic alcohols derived from 2, alpha-C8 (20), beta-C8 (14), and C16 (15), were synthesized and tested; only 15 exhibited substantial in vivo activity.
Assuntos
Antineoplásicos Fitogênicos/síntese química , Animais , Compostos de Epóxi , Hidrólise , Hidroxilação , Leucemia P388/tratamento farmacológico , Camundongos , Oxirredução , Relação Estrutura-AtividadeRESUMO
Verrucarins A (4) and B (5) and verrucarin A acetate, in vivo antileukemic inactive fungal metabolites, have been oxidized with m-chloroperoxybenzoic acid to give verrucarin beta-9,10-epoxides which show high in vivo activity against P388 mouse leukemia.