RESUMO
The convergent and selective preparation of (Z)-monofluoroalkene-based dipeptide isosteres from functionalized fluorosulfones as a cornerstone is described. In this approach, the N-terminal amino group is introduced by a conjugate addition reaction of phthalimide onto fluorinated vinylsulfones containing α-amino-acid side chains while the C-terminal motif is linked to the fluorovinylic peptide bond mimic via the Julia-Kocienski reaction between fluorosulfones and substituted aldehydes bearing α-amino-acid side chains.
Assuntos
PeptidomiméticosRESUMO
A series of fluorine and non-fluorine-substituted C-glucosylidenes (exo-glucals) has been synthesized via a modified Julia olefination. The deprotected exo-glucals were prepared in five steps from commercially available d-gluconolactone. The evaluation of this original family of compounds against a panel of glycosidases showed a highly specific in vitro activity towards mammalian ß-glucosidase depending on the double bond substituents.
Assuntos
Alcenos/química , Inibidores Enzimáticos/farmacologia , Monossacarídeos/farmacologia , beta-Glucosidase/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Glicosídeos , Estrutura Molecular , Monossacarídeos/síntese química , Monossacarídeos/química , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-Atividade , beta-Glucosidase/metabolismoRESUMO
Convenient access to homochiral fluoroalkenes is described via a Julia-Kocienski olefination reaction. The required homochiral fluorosulfone is synthesized by a Mitsunobu reaction from readily available enantiopure secondary alcohols.
Assuntos
Alcenos/química , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Fluorados/síntese química , Álcoois/química , Alquilação , Fluoretos/química , Estrutura Molecular , Estereoisomerismo , Ácidos Sulfúricos/químicaRESUMO
The use of aryl triflates as reaction partners in a palladium-catalyzed domino direct arylation/N-arylation provides a great advantage due to the availability of starting materials. Furthermore, it allows expedient access to biologically interesting benzo[c]phenanthridine alkaloids.