RESUMO
Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.
Assuntos
Ciclopropanos/síntese química , Inibidores Enzimáticos/síntese química , Fucose/análogos & derivados , Ramnose/análogos & derivados , Compostos de Espiro/síntese química , Ciclopropanos/química , Ciclopropanos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fucose/síntese química , Fucose/química , Fucose/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Glicosídeo Hidrolases/metabolismo , Cinética , Espectroscopia de Ressonância Magnética , Rotação Ocular , Ramnose/síntese química , Ramnose/química , Ramnose/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Compostos de Espiro/química , Compostos de Espiro/farmacologia , alfa-L-Fucosidase/antagonistas & inibidores , alfa-L-Fucosidase/metabolismoRESUMO
An efficient route to nonsymmetrical helical menthyl esters by means of an oxidative photocyclization reaction of dissymmetric bis-stilbenes is reported. The developed route allows the introduction of functionality on rings A, E, or F, and the influence of the substituent pattern on the photochemical reaction has been examined. Diastereoselectivity is observed when a double chiral induction strategy with dimenthyl helicene esters synthesized in a 70:30 ratio of isomers is used.
RESUMO
Adenophorine and its 5-deoxy analogue have been identified as natural iminosugars with efficient glycosidase inhibitory effects. The syntheses and biological evaluation of two new series of 5-deoxyadenophorine analogues in their racemic form are reported. The compounds 12e and 13d bearing a C11 and C7 alkyl chain, respectively, were found to be potent inhibitors of the beta-glucosidase from almond with Ki near to 60 microM. The compounds 13a,d which possess a 3,4-cis stereochemistry were efficient on glucosidases but also on the beta-galactosidase, what was not observed with the 3,4-trans series 12.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Glucosamina/análogos & derivados , Alquilação , Inibidores Enzimáticos/química , Galactosidases/antagonistas & inibidores , Galactosidases/metabolismo , Glucosamina/síntese química , Glucosamina/química , Glucosamina/farmacologia , Glucosidases/antagonistas & inibidores , Glucosidases/metabolismo , Imino Açúcares/química , Manosidases/antagonistas & inibidores , Manosidases/metabolismo , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
We report here an efficient synthesis for pyrimidine nucleoside analogues by [4 + 2] cycloaddition reaction. These compounds were obtained by convergent chemistry from glycosyl isothiocyanates 3a-f (pyranoses, furanoses, and dissaccharides) and diazadienium salt 5. In fact, diazapentadienium iodide 5 prepared from vinylthioamide 4 is an efficient intermediate in heterocyclic synthesis and reacts with isothiocyanates 3a-f affording beta-D-uracil analogues 7a-f in good yields and with total regiocontrol. All compounds were fully characterized by IR, HRMS, and 13C and 1H NMR (COSY and HMQC).