Total Synthesis and Absolute Configuration of Macrocidin A, a Cyclophane Tetramic Acid Natural Product
Total Synthesis and Absolute Configuration of Macrocidin A, a Cyclophane Tetramic Acid Natural Product
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DOI：
10.1002/anie.200906362
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Suzuki, Keisuke
中科院分区：
文献类型：
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作者：
Yoshinari, Tomohiro;Ohmori, Ken;Suzuki, Keisuke
Macrocidin A(1)和Macrocidin b(2)是由寄生在加拿大蓟上的微生物巨口瘤（Phoma macrostoma）产生的一个新的植物病原体家族通过广泛的二维核磁共振研究和单晶x射线分析确定了1的有趣结构，其中包括一个安装在环烷骨架中的四羧酸[2]基团，尽管由于天然样品的缺乏，其绝对结构仍有待解决。大杀线虫素对阔叶杂草有显著的除草活性，而对禾草没有显著的除草活性，这使其成为新型除草剂设计的潜在先导。它们的生物活性和新颖的化学结构使这些化合物成为化学合成的重要目标。虽然大环骨架的构建已经解决，但完整结构的合成仍有待实现。在这里，我们描述了第一个用大内酰胺形成然后环化的大cidin A(1)的全合成。方案1概述了我们基于Lacey-Dieckmann环化[4]构建的乙酰四酸片段的反合成分析，这反过来又可以通过分子内捕获可能由二恶英酮前体II热生成的酰基烯类(a)来获得这个关键中间体（II）可能是
Macrocidin A (1) and macrocidinB (2) represent a new family of plant pathogens produced by Phoma macrostoma, a microorganism parasitic to Canadian thistle.[1] The intriguing structure of 1, which includes a tetramic acid [2] group installed in a cyclophane skeleton, was determined by extensive 2D NMR studies and single-crystal X-ray analysis, although the absolute configuration remains to be addressed because of a paucity of the natural sample. The macrocidins have significant herbicidal activity on broadleaf weeds but not on grasses, which makes them a potential lead for new herbicide design. Their biological activity and novel chemical structures have made these compounds attractive targets for chemical synthesis. Whilst construction of the macrocyclic skeleton has been addressed,[3] the synthesis of the full structure remains to be achieved. Herein, we describe the first total synthesis of macrocidin A (1) using macrolactam formation followed by cyclization.Scheme 1 outlines our retrosynthetic analysis based upon the construction of the acyltetramic acid moiety using the Lacey–Dieckmann cyclization [4] of macrolactam I, which in turn would be accessible by the intramolecular trapping of an acylketene species (a) that may be thermally generated from dioxinone precursor II.[5] This key intermediate (II) could be