Total synthesis of palau'amine.
Total synthesis of palau'amine.
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DOI：
10.1002/anie.200907112
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发表时间：
2010-02-01
影响因子：
16.6
通讯作者：
Baran, Phil S.
中科院分区：
文献类型：
--
作者：
Seiple, Ian B.;Su, Shun;Young, Ian S.;Lewis, Chad A.;Yamaguchi, Junichiro;Baran, Phil S.
多环二聚吡咯-咪唑生物碱，如帕劳胺 (1，方案 1)、[1] axinellamine A (2)、[2] 和马沙丁氯化物 (3)[3] 具有令人畏惧的结构和物理属性，包括九个或更多氮原子、八个连续的立体中心、反应性（半）缩醛胺部分、易于氧化的吡咯和高极性、非结晶形态。它们独特的结构一直是全球许多团体众多出版物的焦点，并导致合成方法学的显着进步。 [4]在此类更复杂的成员中，只有 axinellamines（例如 2）[5] 和 Massadines（例如 3）[6] 在高度化学选择性和可控后期氧化反应的发明的帮助下实现了全合成。与其同源物（2 和 3）相比，帕劳胺 (1) 具有独特的化学挑战：吡咯酰胺侧链之一嵌入精致的、六环核心结构，其中包含高度应变的反氮杂双环[3.3。 0]辛烷子结构（天然产物中前所未有）。这无疑是有机化学家迄今为止未能合成帕劳胺 (1) 的一个核心原因，尽管自 1993 年分离和 2007 年结构重新分配以来，已经出现了数十篇博士论文 [7] 和对出版物 [8] 的研究。 [1]在我们的实验室中，为确保特殊的反式 5、5 核 1 的安全而制定的许多有理有据且合乎逻辑的计划都导致了不幸的结果。据推测，六环结构中隐含的高度应变阻碍了仿生闭合（同时进行 N14-C10 和 N1-C6）[4] 或逐步闭合（N14-C10 随后是 N1-C6）的所有尝试。 [9]在这些最初的尝试中吸取的经验教训启发了一种替代策略，最终导致了本文提出的 1 的全面综合。
Polycyclic dimeric pyrrole–imidazole alkaloids such as palauamine (1, Scheme 1),[1] axinellamine A (2),[2] and massadine chloride (3)[3] possess daunting structural and physical attributes, including nine or more nitrogen atoms, eight contiguous stereogenic centers, reactive (hemi) aminal moieties, oxidation-prone pyrroles, and highly polar, non-crystalline morphologies. Their unique structures have been the focus of numerous publications from many groups worldwide, and have led to notable advances in synthetic methodology.[4] Among the more complex members of this class, only the axinellamines (eg 2)[5] and the massadines (eg 3)[6] have succumbed to total synthesis, aided by the invention of a highly chemoselective and controllable late-stage oxidation reaction.Compared to its congeners (2 and 3), palau amine (1) possesses a unique chemical challenge: one of the pyrroleamide sidechains is embedded in an exquisite, hexacyclic core architecture which contains a highly strained transazabicyclo [3.3. 0] octane substructure (unprecedented among natural products). This is undoubtedly a central reason why the synthesis of palau amine (1) has thus far eluded organic chemists despite the dozens of Ph. D. theses [7] and studies towards publications [8] that have appeared since its isolation in 1993 and structural reassignment in 2007.[1] Many wellfounded and logical plans to secure the peculiar trans-5, 5 core of 1 in our laboratory resulted in unfortunate outcomes. Presumably, the high degree of strain implicit in the hexacyclic architecture thwarted all attempts at a biomimetic closure (N14-C10 and N1-C6 simultaneously)[4] or a stepwise closure (N14-C10 followed by N1-C6).[9] The lessons learned during those initial attempts inspired an alternative strategy that ultimately led to the total synthesis of 1 presented herein.
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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：
16.6
作者：
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影响因子：
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影响因子：
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影响因子：
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作者：
Garrido-Hemandez, H;Nakadai, M;Harran, PG
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