Assuntos
Produtos Biológicos/química , Inibidores Enzimáticos/química , Manosidases/antagonistas & inibidores , Pirrolidinas/química , Alcaloides/química , Alcaloides/metabolismo , Sítios de Ligação , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Manosidases/metabolismo , Simulação de Acoplamento Molecular , Ligação Proteica , Estrutura Terciária de ProteínaRESUMO
The preparation of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids using a combination of solid- and solution-phase organic synthesis is described. The key intermediates, enantiopure five- or six-membered tri-O-benzyl cyclic nitrones, were efficiently prepared on solid support from accessible chiral furanosides and pyranosides, respectively. The substituent diversity was achieved by a diastereoselective addition of a variety of Grignard reagents to the cyclic nitrones in solution-phase synthesis. All reaction steps and work-up procedures were modified to allow the use of automated equipment. A 36-membered demonstration library with three diversity elements (core, configuration, and substituent) was prepared in good yield and purity.
