Evolution of a Synthetic Strategy for Complex Polypyrrole Alkaloids: Total Syntheses of Curvulamine and Curindolizine.
Evolution of a Synthetic Strategy for Complex Polypyrrole Alkaloids: Total Syntheses of Curvulamine and Curindolizine.
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DOI：
10.1021/jacs.0c13465
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发表时间：
2021-02-24
影响因子：
15
通讯作者：
Maimone TJ
中科院分区：
文献类型：
--
作者：
Xuan J;Haelsig KT;Sheremet M;Machicao PA;Maimone TJ
最近从弯孢菌和玉米小斑病菌中分离出了结构上前所未有的含有多个富电子吡咯单元的抗菌生物碱。本文记录了旨在获得旗舰代谢物curvulamine和curindolizine的合成计划的进展，这两种代谢物可能分别是C10 N生物合成结构单元的二聚体和三聚体。从curvulamine开始，我们详细介绍了几种策略来合并两个简单的生物启发片段，虽然最终没有成功，但我们采用了基于吡咯并氮杂卓酮构建模块的策略，并改进了这种10π-芳香杂环的合成。然后设计了两步成环过程以形成保守的四环双吡咯结构并进入各种后期中间体;然而，不幸的是，失败的后期脱羧阻碍了弯孢胺的全合成。通过调整我们的成环前体，成功最终发现通过使用氰醇亲核试剂，使10步全合成弯孢胺。然后尝试实现一个仿生耦合curvulamine与一个额外的C10 N片段，以达到curindolizine，最复杂的家庭成员。虽然非生产性的，我们开发了一个14步全合成这种生物碱通过非生物耦合的方法。在这项工作中，努力利用和利用吡咯核的固有反应性，这是一个目标，发现了许多有趣的发现，在化学反应性杂环。
Structurally unprecedented antibacterial alkaloids containing multiple electron-rich pyrrole units have recently been isolated from Curvularia sp. and Bipolaris maydis fungi. This article documents the evolution of a synthetic program aimed at accessing the flagship metabolites curvulamine and curindolizine which are presumably a dimer and trimer of a C10N biosynthetic building block, respectively. Starting with curvulamine, we detail several strategies to merge two simple, bioinspired fragments, which while ultimately unsuccessful, led us toward a pyrroloazepinone building block-based strategy and an improved synthesis of this 10π-aromatic heterocycle. A two-step annulation process was then designed to forge a conserved tetracyclic bis-pyrrole architecture and advanced into a variety of late-stage intermediates; unfortunately, however, a failed late-stage decarboxylation thwarted the total synthesis of curvulamine. By tailoring our annulation precursors, success was ultimately found through the use of a cyanohydrin nucleophile which enabled a 10-step total synthesis of curvulamine. Attempts were then made to realize a biomimetic coupling of curvulamine with an additional C10N fragment to arrive at curindolizine, the most complex family member. Although unproductive, we developed a 14-step total synthesis of this alkaloid through an abiotic coupling approach. Throughout this work, effort was made to harness and exploit the innate reactivity of the pyrrole nucleus, an objective which has uncovered many interesting findings in the chemistry of this reactive heterocycle.
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氧化进入倍半萜：（+） - 假氨酸蛋白酶的对映体合成。
影响因子：
15
作者：
Hung K;Condakes ML;Morikawa T;Maimone TJ
通讯作者：
Maimone TJ
Curvulamine，一种新型抗菌生物碱，包含来自弯孢菌属物种的两个未描述的单位
影响因子：
5.2
作者：
Han, Wen Bo;Lu, Yan Hua;Tan, Ren Xiang
通讯作者：
Tan, Ren Xiang
影响因子：
64.8
作者：
Baran, Phil S.;Maimone, Thomas J.;Richter, Jeremy M.
通讯作者：
Richter, Jeremy M.
影响因子：
15
作者：
Candish, Lisa;Teders, Michael;Glorius, Frank
通讯作者：
Glorius, Frank
DOI：
10.1039/jr9500002804
发表时间：
1950-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY
影响因子：
--
作者：
HAWKINS, EGE;YOUNG, DP
通讯作者：
YOUNG, DP