Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement
Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement
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DOI：
10.1002/chem.201601605
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发表时间：
2016-07-25
影响因子：
4.3
通讯作者：
Moody, Christopher J.
中科院分区：
文献类型：
--
作者：
David, Nadege;Pasceri, Raffaele;Moody, Christopher J.
本文报道了海洋天然产物重氮酰胺A的一种简短的全合成方法。该路线是基于吲哚氧化重排，和一些选项进行了研究，涉及酪氨酸或恶唑片段氧化后的开链或大环前体的迁移。最后一条路线是从7-溴吲哚开始，依次在C-2位偶联一个恶唑片段，然后在C-3位偶联一个酪氨酸片段。随着关键的2，3-二取代吲哚的容易到手，大环内酰胺的形成为关键的氧化重排为3，3-二取代羟吲哚奠定了基础。尽管伴随形成了不需要的吲哚氧基异构体，但在脱保护后，该合成成功地递送了关键的羟吲哚中间体，从而完成了重氮酰胺A的正式全合成。
A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A.