RESUMO
5-Substituted-2-furan methanols 1a-c are subject to enantioselective carbonyl allylation, crotylation and tert-prenylation upon exposure to allyl acetate, alpha-methyl allyl acetate, or 1,1-dimethylallene in the presence of an ortho-cyclometalated iridium catalyst modified by (R)-Cl,MeO-BIPHEP, (R)-C3-TUNEPHOS, and (R)-C3-SEGPHOS, respectively. In the presence of 2-propanol, but under otherwise identical conditions, the corresponding substituted furfurals 2a-c are converted to identical products of allylation, crotylation, and tert-prenylation. Optically enriched products of carbonyl allylation, crotylation, and reverse prenylation 3b, 4b, and 5b were subjected to Achmatowicz rearrangement to furnish the corresponding gamma-hydroxy-beta-pyrones 6a-c, respectively, with negligible erosion of enantiomeric excess.
Assuntos
Acetatos/química , Compostos Alílicos/química , Furaldeído/química , Furanos/química , Irídio/química , Metanol/química , Pironas/química , Catálise , Hidrogenação , Estrutura Molecular , EstereoisomerismoRESUMO
Here, we describe a series of readily obtainable benzophenone derivatives with antimalarial and antitrypanosomal activity. The most active compounds display submicromolar activity against Plasmodium falciparum. Micromolar activity is obtained against Trypanosoma brucei. Main problem of the compounds is low selectivity. However, there are indications that separation of antimalarial and cytotoxic activity might by possible. In addition, some compounds inhibit human ABC transporter with nanomolar activity.
Assuntos
Amidas/química , Amidas/farmacologia , Antimaláricos/síntese química , Benzofenonas/química , Plasmodium falciparum/efeitos dos fármacos , Sulfonamidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Amidas/síntese química , Antimaláricos/química , Antimaláricos/farmacologia , Benzofenonas/síntese química , Benzofenonas/farmacologia , Concentração Inibidora 50 , Malária/tratamento farmacológico , Malária/parasitologia , Testes de Sensibilidade Parasitária , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/metabolismoRESUMO
Previously we described a series of 5-acylaminobenzophenones with considerable antimalarial activity. Unfortunately, most compounds also displayed high cytotoxicity resulting in low selectivity towards malaria parasites. Through the replacement of the 5-acylamino moiety by simple chlorine and further modifications of the 2-acylamino residue we could obtain inhibitors with improved selectivity towards malaria parasites combined with an acceptable reduction of antimalarial activity.