Total synthesis of thiostrepton. Assembly of key building blocks and completion of the synthesis
Total synthesis of thiostrepton. Assembly of key building blocks and completion of the synthesis
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DOI：
10.1021/ja052934z
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发表时间：
2005-08-10
影响因子：
15
通讯作者：
Nevalainen, M
中科院分区：
文献类型：
--
作者：
Nicolaou, KC;Zak, M;Nevalainen, M
描述了硫链丝菌肽(1)的全合成的完成。合成从关键构建模块 2-5 开始，这些构建模块被组装成不断生长的底物，最终产生目标分子。因此，在适当的操作后，脱氢哌啶肽核心2与噻唑啉-噻唑片段3偶联，所得产物进一步形成具有噻唑啉-噻唑大环的中间体11。然后依次掺入双脱氢丙氨酸尾部当量4和喹哪啶酸片段5，并将由此获得的产物进一步精制以形成分子的第二个大环。系统地研究并克服了沿途遇到的几个障碍，最终为中间体 20、32、44、45 和 46 开辟了通往目标天然产物 1 的道路。
The completion of the total synthesis of thiostrepton (1) is described. The synthesis proceeded from key building blocks 2-5, which were assembled into a growing substrate that finally led to the target molecule. Thus, the dehydropiperidine peptide core 2 was, after appropriate manipulation, coupled to the thiazoline-thiazole fragment 3, and the resulting product was advanced to intermediate 11 possessing the thiazoline-thiazole macrocycle. The bis-dehydroalanine tail equivalent 4 and the quinaldic acid fragment 5 were then sequentially incorporated, and the products so obtained were further elaborated to forge the second macrocycle of the molecule. Several roadblocks encountered along the way were systematically investigated and overcome, finally opening the way, through intermediates 20, 32, 44, 45, and 46, to the targeted natural product, 1.