Total synthesis of microsclerodermin E
Total synthesis of microsclerodermin E
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DOI：
10.1002/anie.200352423
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Ma, DW
中科院分区：
文献类型：
--
作者：
Zhu, JD;Ma, DW
在海洋生物中，石质海绵以其产生多种生物活性代谢物的能力而闻名福克纳和他的同事从几种海绵微硬皮病（Microscleroderma sp.）和Theonella sp.中分离出一系列环状肽，命名为microsclerodermins a - i .[2]在结构上，每一个都显示出几个独特的特征，包括一个23元的环六肽核心，包含一个非常复杂的b氨基酸和三个其他非天然氨基酸残基。初步研究表明，所有这些化合物都具有有趣的抗真菌活性，其中一些具有有效的抗肿瘤特性，[2,3]但由于它们的相对稀缺性，对其生物活性的进一步评估受到阻碍。微硬皮质所表现出的生物活性和结构复杂性引起了合成化学家的广泛关注。然而，尽管对这些化合物的合成已经有了一些报道，但尚未合成出该家族的成员。在此，我们希望描述我们的微硬皮蛋白e的全合成，合成的值得注意的元素是其b-氨基酸片段的简洁组装，吡咯烷酮片段的组装，几乎没有外消旋，以及在Gly-GABOB位点有效的大环化。
Lithistid sponges are well-known among marine organisms for their ability to produce a diverse array of biologically active metabolites.[1] From several species of the lithistid sponge Microscleroderma sp. and Theonella sp., Faulkner and co-workers have isolated a series of cyclic peptides named microsclerodermins A–I.[2] Structurally, each of them was shown to display several unique features, including a 23-membered cyclic hexapeptide core, featuring a very complex b-amino acid and three other unnatural amino acid residues. Preliminary studies have indicated that all these compounds possess intriguing antifungal activities and some of them show potent antitumor properties,[2, 3] but further evaluation of their biological activities has been hampered by their relative scarcity. The biological activities and the structural complexity exhibited by the microsclerodermins have attracted much attention within the community of synthetic chemists. However, although some synthetic efforts towards these compounds have been reported,[4] no member of this family has been synthesized yet. Herein we wish to describe our total synthesis of microsclerodermin E. Notable elements of the synthesis are the concise assembly of its b-amino acid fragment, the assembly of the pyrrolidinone fragment with little racemization, and the effective macrocyclization at the Gly-GABOB site.