Total Synthesis and Conformational Analysis of Apratoxin C
Total Synthesis and Conformational Analysis of Apratoxin C
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DOI：
10.1021/jo501130b
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发表时间：
2014-09-05
影响因子：
3.6
通讯作者：
Doi, Takayuki
中科院分区：
文献类型：
--
作者：
Masuda, Yuichi;Suzuki, Jun;Doi, Takayuki
利用我们开发的阿曲毒素A合成策略，实现了阿曲毒素C的全合成。为了阐明构象与活性之间的关系，采用核磁共振波谱法对阿曲毒素C的三级结构进行了分析。我们得到了37个ROE和5（3）J（H，H）值，分别转化为距离和二面角约束。采用距离几何方法进行了限制性构象搜索的分子模拟。最低能量结构表明，在C37的甲基和异丙基在C39发挥关键作用，在维持构象，而在C34的甲基没有。此外，我们证实，黄曲霉毒素A和C具有相似的构象，提供了一个可能的解释，他们几乎相等的细胞毒性。
Total synthesis of apratoxin C, a cyanobacterial cyclodepsipeptide with highly potent cytotoxicity against some cancer cell lines, was achieved using the apratoxin A synthetic strategy developed by us. To elucidate the relationship between conformation and activity, the tertiary structure of apratoxin C was analyzed by NMR spectroscopy. We obtained 37 ROEs and five (3)J(H,H) values, which were translated into distance and dihedral angle constraints, respectively. Molecular modeling was performed with a restrained conformational search by a distance geometry method. The lowest energy structure indicated that the methyl group at C37 and the isopropyl group at C39 play critical roles in maintaining the conformation, whereas the methyl group at C34 does not. Moreover, we confirmed that apratoxin A and C possess similar conformations, providing a likely explanation for their nearly equivalent cytotoxicities.