The Synthesis and Antimicrobial Activity of Heterocyclic Derivatives of Totarol.

The Synthesis and Antimicrobial Activity of Heterocyclic Derivatives of Totarol.
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DOI:
10.1021/ml3001775
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发表时间:
2012-08-28
影响因子:
4.2
通讯作者:
Shaw, Jared T.
Shaw, Jared T.
中科院分区:
医学3区
文献类型:
--
作者:
Kim, Michelle B.;O'Brien, Terrence E.;Moore, Jared T.;Anderson, David E.;Foss, Marie H.;Weibel, Douglas B.;Ames, James B.;Shaw, Jared T.

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介绍了二萜类生育醇的合成及其杂环类似物的抗菌活性。一种先进的A环上含酮的合成中间体被用来连接稠合杂环,并通过从头合成在B环上进行了碳到氮原子的取代。带有吲哚的A环类似物第一次展示了相对于母体天然产物的增强的抗菌活性。初步实验表明,吲哚类似物并不针对细菌细胞分裂蛋白FtsZ,这一点曾被认为是针对totarol的。
The synthesis and antimicrobial activity heterocyclic analogs of the diterpenoid totarol are described. An advanced synthetic intermediate with a ketone on the A-ring is used to attach fused heterocycles and a carbon-to-nitrogen atom replacement is made on the B-ring by de novo synthesis. A-ring analogs with an indole attached exhibit, for the first time, enhanced antimicrobial activity relative to the parent natural product. Preliminary experiments demonstrate that the indole analogs do not target the bacterial cell division protein FtsZ as had been hypothesized for totarol.
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