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Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors.

ABSTRACT: The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-?-lactamase inhibitors is described. The reaction of ?-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.

SUBMITTER: Saiz C

PROVIDER: S-EPMC5451161 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors.

Saiz Cecilia C Villamil Valentina V González Mariano M MM Rossi Ma Agustina MA Martínez Lorena L Suescun Leopoldo L Vila Alejandro J AJ Mahler Graciela G

Tetrahedron, asymmetry 20161128 1

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 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 oxazolidinylthiazolidine ...[more]

PMID: 28579699

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