RESUMO
The total synthesis of (-)-amidepsine B, a potent diacylglycerol acyltransferase inhibitor, has been achieved. This synthetic study resulted in the revision of the previously assigned stereostructure of the natural amidepsine B and determined the absolute configuration.
Assuntos
Inibidores Enzimáticos/síntese química , Hidroxibenzoatos/síntese química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Diacilglicerol O-Aciltransferase/antagonistas & inibidores , Inibidores Enzimáticos/química , Hidroxibenzoatos/química , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18-membered ring after esterification between two segments. A detailed examination of the macrocyclization led us to the samarium(II) iodide-mediated intramolecular Reformatsky-type reaction as the most efficient synthetic approach. The two key segments were synthesized through regioselective methylation, directed hydrogenation, stereoselective Reformatsky-type reaction, and MgBr2.Et2O-mediated chelation-controlled allylation.
