Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors

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• 作者：Cecilia Saiz^a ; ^{csaiz@fq.edu.uy} ; Valentina Villamil^a ; Mariano M. Gonzá ; lez^b ; Ma. Agustina Rossi^b ; Lorena Mart&iacute ; nez^c ; Leopoldo Suescun^c ; Alejandro J. Vila^b ; Graciela Mahler^a ; ^{gmahler@fq.edu.uy}
• 刊名：Tetrahedron: Asymmetry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：28
• 期：1
• 页码：110-117
• 全文大小：2084 K
• 卷排序：28

文摘

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.