Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone.
Conformation-activity relationships in polyketide natural products. Towards the biologically active conformation of epothilone.
复制标题
聚酮天然产物中的构象-活性关系。
DOI：
10.1039/b312213c
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Pabba,PraveenK
中科院分区：
文献类型：
--
作者：
Taylor,RichardE;Chen,Yue;Galvin,GabrielM;Pabba,PraveenK
测定了具有生物活性的聚酮化合物埃坡霉素的构象-活性关系。基于计算机的分子模拟和高场NMR技术提供了埃坡霉素1和2的解决方案的偏好。对于C1-C8聚丙酸酯区域，两个构象家族，构象1和2，已被确定为在极性和非极性溶剂中具有显著的群体。在C11-C15区域，观察到额外的灵活性，并已确定两个局部构象是重要的，构象3和4。已经设计并合成了具有改变的构象分布的埃博霉素类似物。构象分析和生物测定的结果已被关联，以提供更多的了解埃坡霉素类天然产物的生物活性构象。构象-活性关系已被证明是结构-活性数据的重要补充。
The conformation–activity relationships for the biologically active polyketide, epothilone, have been determined. Computer-based molecular modeling and high field NMR techniques have provided the solution preferences for epothilones 1 and 2. For the C1–C8 polypropionate region, two conformational families, conformers 1 and 2, have been identified as having significant populations in polar and non-polar solvents. In the C11–C15 region, additional flexibility was observed and two local conformations have been identified as important, conformers 3 and 4. Epothilone analogues with altered conformational profiles have been designed and synthesized. Conformational analysis and the results of biological assays have been correlated to provide increased understanding of the biologically active conformation for the epothilone class of natural product. Conformation–activity relationships have been shown to be an important complement to structure–activity data.