largazole 及其衍生物的全合成及生物评价，这些衍生物对癌细胞具有良好的选择性。
Total synthesis and biological evaluation of largazole and derivatives with promising selectivity for cancers cells.
机构信息
Guangzhou Institute of Biomedicine and Health, CAS, Guangzhou 510663, PR China.
出版信息
Org Lett. 2010 Mar 19;12(6):1368-71. doi: 10.1021/ol100308a.
Abstract
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.
摘要
本文描述了天然物质 largazole 的高效全合成。利用该策略，开发了一个 largazole 类似物的小文库。构效关系研究表明，侧链中烯烃的几何形状是关键的。 largazole 的顺式烯烃类似物完全没有活性，而反式烯烃类似物具有很强的抗增殖作用。最重要的是， largazole 中的缬氨酸被酪氨酸取代后，对人癌细胞的选择性比人正常细胞高 100 多倍。
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