Synthesis of marine alkaloids from the oroidin family
Synthesis of marine alkaloids from the oroidin family
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DOI：
10.1002/anie.200801793
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Riedrich, Matthias
中科院分区：
文献类型：
--
作者：
Arndt, Hans-Dieter;Riedrich, Matthias
多杂环、富氮生物碱可能是有机合成中最具挑战性的合成目标之一。在这方面，兰花甙类生物碱最近受到了广泛关注（方案 1），[1] 其中 sceptrin (1)、axinellamines（2 和 3）、palau amine (4) 和ageliferin (5)。这些海洋天然产物源自一种前体，即 1971 年首次发现的相当不起眼的吡咯并咪唑烯烃 oroidin (6)。 [2]目前认为，6 个连续官能化的二聚化产生了一系列令人印象深刻的密集官能化、高度氧化、多环 oroidin 生物碱。 [1e, 3] 这些分子的相似性及其经常同时出现表明了共同的生物合成途径，并且进一步表明从一个简单的前体生成了不同的天然产物化合物“库”。 [4]直到最近，帕劳胺 (4) 还不能很好地融入这一统一的图景，主要是由于立体化学原因。在最初的工作中，两个五元环的连接被指定为顺式。[5]然而，彻底的光谱研究 [6, 1e] 最近得到了合成的补充（参见下文），[7] 这同样表明 4 中的 C-11/C-12 环融合处于热力学上不太稳定的反式构型（如方案 1 所示）。这种结构修改现在使帕劳胺成为甲醚生物碱组的正式成员，并带来了在不久的将来可能开发其全合成综合策略的希望。所有这些吡咯-咪唑生物碱都具有四元、五元或六元中心碳环和侧链杂环的单独连接性。这些独特的模式激发了许多合成努力，并为每个支架带来了独特的解决方案（方案 2）。 [8]在一项关于生物合成的早期假说中，ageliferins 7 的六元环被认为是由 [4 2] 环加成产生的。[3a] 这首先由 Ohta 等人在合成中实现。(8!7)。[9] Chen 和 Tan 开发了 MnIII 促进的咪唑酮 9 自由基级联环化。 [10] Baran 等人在 5 的全合成中。成功实现了四元环前体 sceptrin (1) 在高温条件下双环放大到 5。 [11] sceptrin 支架 10 本身是通过 [2+2] 光环加成，例如 (E)-1, 4-二氯-2-丁烯和马来酸酐 [12] 或通过光化学可接近的 oxaquadricyclane 11 的碎裂而制成的。 [13]
Polyheterocyclic, nitrogen-rich alkaloids probably rank among the most challenging synthetic targets in organic synthesis. In this regard the oroidin class of alkaloids has received much attention recently (Scheme 1),[1] among them sceptrin (1), the axinellamines (2 and 3), palau amine (4), and ageliferin (5). These marine natural products arise from one precursor, the rather inconspicuous pyrrolo-imidazole alkene oroidin (6) first identified in 1971.[2] Dimerization of 6 and consecutive functionalizations are currently believed to give rise to this impressive array of densely functionalized, highly oxidized, polycyclic oroidin alkaloids.[1e, 3] The similarity of these molecules and their often simultaneous occurrence is indicative of common biosynthetic pathways, and furthermore suggests the generation of a divergent natural product compound “library” from one simple precursor.[4] Until lately, palau amine (4) did not fit well into this unifying picture, mostly for stereochemical reasons. In the original work the junction of the two five-membered rings had been assigned as cis.[5] However, thorough spectroscopic investigation [6, 1e] was recently complemented by synthesis (vide infra),[7] which likewise suggested the C-11/C-12 ring fusion in 4 to be in the thermodynamically less stable trans configuration (as shown in Scheme 1). This structural revision now makes palau amine a full member of the oroidin alkaloid group and raises hope that integrative strategies for their total synthesis might be developed in the near future. All these pyrrole–imidazole alkaloids feature a four-, five-, or six-membered central carbocyclic ring and an individual connectivity of the pendant side chain heterocycles. These unique patterns have stimulated many synthetic efforts and led to distinct solutions for each of the scaffolds (Scheme 2).[8] In one early hypothesis on the biosynthesis, the six-membered ring of the ageliferins 7 was proposed to arise from a [4 2] cycloaddition.[3a] This was implemented in synthesis first by Ohta etal.(8! 7).[9] A MnIII-promoted radical cascade annulation from the imidazolone 9 was developed by Chen and Tan.[10] In their total synthesis of 5, Baran et al. successfully implemented a double ring-enlargement of the fourmembered-ring precursor sceptrin (1) to 5 under hightemperature conditions.[11] The sceptrin scaffold 10 itself has been elaborated by [2+ 2] photocycloadditions, for instance from (E)-1, 4-dichloro-2-butene and maleic anhydride [12] or by fragmentation of the photochemically accessible oxaquadricyclane 11.[13]