What is amphidinolide V?: Report on a likely conquest
What is amphidinolide V?: Report on a likely conquest
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DOI：
10.1002/anie.200701640
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Fluegge, Susanne
中科院分区：
文献类型：
--
作者：
Fuerstner, Alois;Larionov, Oleg;Fluegge, Susanne
迄今为止，已经从实验室培养的前沟藻的甲藻中分离出30多种大环内酯。[1]尽管它们的共同来源和对各种癌细胞系的一致的高细胞毒性，个别的“amphidinolides”在结构上是相当多样的，因此激发了许多合成方法。[2，3]该系列中最稀有的成员之一是amphidinolideV（收获藻类湿重的0.00005%），基于不超过0.2 mg样品的光谱数据提出了其结构1（方案1）。[4]As作为我们正在进行的海洋生物活性天然产品计划的一部分，[5] amphidinidine V被选为进一步评估的目标。为此，寻求一种灵活的入口，以提供有意义的数量的这种稀缺的代谢物用于测试，并允许在稍后阶段对其分子结构进行系统性修改。据设想，1的独特的s-反式二烯单元，由C-4和C-5处的邻位外亚甲基分支跨越，将在这方面提供独特的机会。如果通过一系列闭环炔复分解（RCAM）[6]和随后所得环炔的分子间烯炔复分解形成，
More than 30 macrolides have been isolated to date from laboratory-cultured dinoflagellates of the Amphidinium sp.[1] Despite their common origin and a uniformly high cytotoxicity against various cancer cell lines, the individual “amphidinolides” are structurally quite diverse and have therefore inspired many synthetic approaches toward them.[2, 3] One of the rarest members of this series is amphidinolideV (0.00005% of the wet weight of the harvested algae), for which structure 1 (Scheme 1) was proposed on the basis of the spectroscopic data of a sample of no more than 0.2 mg.[4]As part of our ongoing program on bioactive natural products of marine origin,[5] amphidinolide V was chosen as a target for further evaluation. To this end, a flexible entry was sought that would provide meaningful amounts of this scarce metabolite for testing, and allow for systematic modification of its molecular edifice at a later stage. It was envisaged that the distinctive s-trans diene unit of 1, spanned by the vicinal exo-methylene branches at C-4 and C-5, would provide a unique opportunity in this regard. If formed by a sequence of ring-closing alkyne metathesis (RCAM)[6] and subsequent intermolecular enyne metathesis of the resulting cycloalkyne