info:eu-repo/semantics/article
Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors
Fecha
2017-01Registro en:
Saiz, Cecilia; Villamil, Valentina; Gonzalez, Mariano Martin; Rossi, María Agustina; Martínez, Lorena; et al.; Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors; Pergamon-Elsevier Science Ltd; Tetrahedron: Asymmetry; 28; 1; 1-2017; 110-117
0957-4166
CONICET Digital
CONICET
Autor
Saiz, Cecilia
Villamil, Valentina
Gonzalez, Mariano Martin
Rossi, María Agustina
Martínez, Lorena
Suescun, Leopoldo
Vila, Alejandro Jose
Mahler, Graciela
Resumen
The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-β-lactamase inhibitors is described. The reaction of β-aminoalcohols and 2,5-dihydroxy-1,4-dithiane led to oxazolidinylthiazolidines and/or dithioazabicycles as the main products. The distribution pattern depends mainly on the aminoalcohol substituents. In a one-pot reaction, four new bonds are formed in good yields and with high atom efficiency. When the oxazolidinylthiazolidines are formed, two stereogenic centres are generated with high enantiospecificity. The reaction mechanism is discussed based on crystallographic data and interconversion studies. Two oxazolidinylthiazolidines were evaluated as inhibitors of the potent lactamase NDM-1 and compound 4f displayed competitive inhibition with Ki = 1.6 ± 0.6 μM.