Total synthesis of N14-desacetoxytubulysin H
Total synthesis of N14-desacetoxytubulysin H
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DOI：
10.1021/ol070415q
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发表时间：
2007-04-12
期刊：
影响因子：
5.2
通讯作者：
Wang, Zhiyong
中科院分区：
文献类型：
--
作者：
Wipf, Peter;Wang, Zhiyong
[图]用20步制备了管溶素H的n -14去乙酰氧基类似物，总收率为2.1%。我们的策略是添加一个噻唑阴离子来组装C(10)-C（11）键上的管缬氨酸残基，以及N-5、N-14和N-17上的酰化。这种迭代耦合方法，以及去除N-14处不稳定的N， o -缩醛，可以合成类似物，用于详细研究这类强效微管蛋白干扰物的结构-活性关系。
[GRAPHICS]The N-14-desacetoxy analogue of tubulysin H was prepared in 20 steps and 2.1% overall yield. Our strategy features a thiazole anion addition to assemble the tubuvaline residue at the C(10)-C(11) bond, as well as acylations at N-5, N-14, and N-17. This iterative coupling approach, as well as the removal of the labile N,O-acetal at N-14, enables the synthesis of analogues for detailed studies of structure-activity relationships in this family of potent tubulin disrupters.