A concise total synthesis of the azaphenanthrene alkaloid eupolauramine
A concise total synthesis of the azaphenanthrene alkaloid eupolauramine
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DOI：
10.1021/jo0105944
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发表时间：
2001-11-30
影响因子：
3.6
通讯作者：
Grandclaudon, P
中科院分区：
文献类型：
--
作者：
Hoarau, C;Couture, A;Grandclaudon, P
采用金属化-环合组合策略，完成了氮杂菲生物碱eupolauramine 1的六步全合成。合成路线首先涉及通过芳炔介导的磷酸化吡啶甲酰胺7的环化和随后的去磷酸化来构建氮杂异吲哚啉酮9。9的金属化，然后连接羟基苄基附件和E1 CB反消除允许形成唯一的E-形式的卤代芳基亚甲基氮杂异吲哚啉酮4。氧化自由基环化引起的氮杂菲骨架和区域选择性溴化3诱导的溴原子在6-位的氮杂菲内酰胺的掺入。最终取代的溴原子2的甲氧基功能通过顺序transmetalation，原位氧化，和O-甲基化的酚衍生物14完成的目标天然产物eupolauramine的合成。
A six-step total synthesis of the azaphenanthrene alkaloid eupolauramine 1 has been achieved using combinational metalation-cyclization tactics. The synthetic route involved first the construction of the azaisoindolinone 9 by aryne-mediated cyclization of he phosphorylated pyridocarboxamide 7 and subsequent dephosphorylation. Metalation of 9 followed by connection of the hydroxybenzyl appendage and E1CB anti-elimination allowed the formation of the halogenoarylmethylene azaisoindolinone 4 in the exclusive E-form. Oxidative radical cyclization gave rise to the azaphenanthrene skeleton and regioselective bromination of 3 induced the incorporation of the bromine atom at the 6-position of the azaphenanthrene lactam. Ultimate replacement of the bromine atom of 2 by the methoxy functionality by sequential transmetalation, in situ oxidation, and O-methylation of the phenolic derivative 14 completed the synthesis of the target natural product eupolauramine.