Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides
Synthesis, configurational stability and stereochemical biological evaluations of (S)- and (R)-5-hydroxythalidomides
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DOI：
10.1016/j.bmcl.2009.02.108
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发表时间：
2009-07-15
影响因子：
2.7
通讯作者：
Sasaki, Takuma
中科院分区：
文献类型：
--
作者：
Yamamoto, Takeshi;Shibata, Norio;Sasaki, Takuma
利用HMDS/ZnBr 2诱导的酰亚胺化反应作为关键反应，首次实现了沙利度胺主要代谢产物之一（S）-和（R）-5-羟基沙利度胺的不对称合成。5-羟基沙利度胺被认为是构型更稳定，比沙利度胺在生理pH值。立体化学生物效应的沙利度胺和5-羟基沙利度胺的抗血管生成和抗肿瘤活性也进行了研究，使用外消旋体和纯对映体。(C)2009爱思唯尔有限公司保留所有权利。
The first asymmetric synthesis of (S)- and (R)-5-hydroxythalidomides, one of thalidomide's major metabolites, was achieved using HMDS/ZnBr2-induced imidation as a key reaction. 5-Hydroxythalidomide was found to be configurationally more stable than thalidomide at physiological pH. Stereochemical biological effects of thalidomide and 5-hydroxythalidomide on anti-angiogenesis and antitumor activities were also investigated using racemic and pure enantiomers. (C) 2009 Elsevier Ltd. All rights reserved.