Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues
Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues
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DOI：
10.1021/ja983788i
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发表时间：
1999-03-17
影响因子：
15
通讯作者：
Rosen, N
中科院分区：
文献类型：
--
作者：
Edmondson, S;Danishefsky, SJ;Rosen, N
标题化合物的全合成已完成。一个关键步骤是通过N-溴代丁二酰亚胺的作用，将β-咔啉衍生物氧化重排为氧化吲哚。从这一点出发，介绍了一种二酮基哌嗪。硫代苯基是异丙叉基的前体。以甲氧基色氨酸衍生物为起点的相同类型的化学实现导致了母体结构。此外，研究还表明，螺环前列腺素A的异丙叉侧链不是生物活性所必需的。此外，三个缺乏二酮基哌嗪系统的类似物被证明是非常有效的细胞周期抑制剂。
The total synthesis of the title compound has been accomplished. A key step involves the oxidative rearrangement of the beta-carboline derivative to an oxindole via the action of N-bromosuccinimide. From this point, a diketopiperazine was introduced. A thiophenyl group served as a precursor of the isopropylidene function. Implementation of the same sort of chemistry starting with a methoxytryptophan derivative led to the parent structures. Furthermore, it was shown that the difficultly accessible isopropylidene side chain of spirotryprostatin A is not necessary for biological activity. Moreover, three analogues lacking the diketopiperazine system were shown to be quite active as cell cycle inhibitors.