RESUMO
C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins bearing O/N-glycosidic linkages, and are thus of great therapeutical potential. Herein, we disclose a protocol for the syntheses of vinyl C-glycosyl amino acids and peptides, employing a nickel-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with common glycosyl bromides. It accommodates a wide scope of the coupling partners, including complex oligosaccharide and peptide substrates. The resultant vinyl C-glycosyl amino acids and peptides, which bear common O/N-protecting groups, are amenable to further transformations, including elongation of the peptide and saccharide chains.
Assuntos
Alcinos/química , Aminoácidos/química , Glicosídeos/química , Níquel/química , Peptídeos/química , Brometos/química , Sequência de Carboidratos , Catálise , Dissacarídeos/química , Glicopeptídeos/síntese química , Glicopeptídeos/química , Glicosídeos/síntese química , Glicosilação , Modelos Químicos , Estrutura Molecular , Monossacarídeos/química , OxirreduçãoRESUMO
Four new analogues of brefeldin A named 7, 7-dimethoxybrefeldin C (3), 6ß-hydroxybrefeldin C (4), 4-epi-15-epi-brefeldin A (5), 4-epi-8α-hydroxy-15-epi-brefeldin C (6), together with four known analogues (1, 7-9) were isolated from a fermentation of the sediment-derived fungus Penicillium sp. DT-F29. The structures of these compounds were elucidated on the basis of extensive spectroscopic and chemical methods. In the bioactivity assays, only compounds 1 and 8 showed significant inhibitory activities against human lung adenocarcinoma cell. In addition, compound 1 was first reported for the potent ability to reactivate latent HIV with EC50 value of 0.03 µM.