Total Synthesis and Biological Evaluation of Largazole and Derivatives with Promising Selectivity for Cancers Cells

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• 作者：Xin Zeng ; Biaolin Yin ; Zheng Hu ; Chenzhong Liao ; Jinglei Liu ; Shang Li ; Zheng Li ; Marc C. Nicklaus ; Guangbiao Zhou ; Sheng Jiang
• 刊名：Organic Letters
• 出版年：2010
• 出版时间：March 19, 2010
• 年：2010
• 卷：12
• 期：6
• 页码：1368-1371
• 全文大小：237K
• 年卷期：v.12,no.6(March 19, 2010)
• ISSN：1523-7052

文摘

The efficient total synthesis of the natural substance largazole is described. Using this strategy, a small library of largazole analogs was developed. Structure−activity relationship studies suggested that the geometry of the alkene in the side chain is critical. While the largazole’s analogues with trans-alkene are potent for the antiproliferative effect, those with cis-alkene are completely inactive. Most importantly, replacement of valine with tyrosine in largazole increased selectivity toward human cancer cells over human normal cells more than 100-fold.