Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors.
Tetrahedron Asymmetry
; 28(1): 110-117, 2017 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-28579699
ABSTRACT
The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-ß-lactamase inhibitors is described. The reaction of ß-aminoalcohols and 2,5-dihydroxy-1,4-dithiane led to oxazolidinylthiazolidines and/or dithia-azabicycles 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Tetrahedron Asymmetry
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Uruguai