Enantioselective synthesis of new oxazolidinyithiazolidines as enzyme inhibitors
Enantioselective synthesis of new oxazolidinyithiazolidines as enzyme inhibitors
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DOI：
10.1016/j.tetasy.2016.11.002
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发表时间：
2017-01-15
影响因子：
--
通讯作者：
Mahler, Graciela
中科院分区：
文献类型：
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作者：
Saiz, Cecilia;Villamil, Valentina;Mahler, Graciela
描述了新的恶唑烷基噻唑烷双环，双噻唑烷的氧类似物，也称为金属-β-内酰胺酶抑制剂的合成。β-氨基醇与2，5-二羟基-1，4-硫杂环丁烷的反应主要生成恶唑烷基噻唑烷和/或二硫代氮杂双环。分布模式主要取决于氨基醇取代基。在一锅反应中，以良好的产率和高原子效率形成四个新键。当形成恶唑烷基噻唑烷时，产生具有高对映体特异性的两个立体中心。根据晶体学数据和相互转化研究讨论了反应机理。评价了两种恶唑烷基噻唑烷作为强效内酰胺酶NDM-1的抑制剂，化合物4f显示出竞争性抑制，Ki = 1.6 +/-0.6 μ M。(C)2016爱思唯尔有限公司版权所有。
The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-beta-lactamase inhibitors is described. The reaction of beta-aminoalcohols and 2,5-dihydroxy-1,4-ithiane led to oxazolidinyithiazolidines 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 oxazolidinyithiazolidines are formed, two stereogenic centres are generated with high enantiospecificity. The reaction mechanism is discussed based on crystallographic data and interconversion studies. Two oxazolidinyithiazolidines were evaluated as inhibitors of the potent lactamase NDM-1 and compound 4f displayed competitive inhibition with K-i = 1.6 +/- 0.6 mu M. (C) 2016 Elsevier Ltd. All rights reserved.