Total synthesis of (+)-haplophytine.
Total synthesis of (+)-haplophytine.
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DOI：
10.1002/anie.200902192
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发表时间：
2009-09
影响因子：
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通讯作者：
H. Ueda;H. Satoh;Koji Matsumoto;Kenji Sugimoto;T. Fukuyama;H. Tokuyama
中科院分区：
文献类型：
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作者：
H. Ueda;H. Satoh;Koji Matsumoto;Kenji Sugimoto;T. Fukuyama;H. Tokuyama
尽管近年来在全合成领域取得了许多令人印象深刻的成就，但许多天然产物已被证明顽固地抵抗其进步。其中之一是haplophytine（1，方案1a），它只是最近才屈服于合成以下的优雅工作福山，德山和同事。Haplophytine首先由Snyder及其同事于1952年分离，并被鉴定为野生花卉Haplophyton cimicidum的主要生物活性成分，几个世纪以来阿兹特克人和随后的中美洲定居者因其杀虫特性而受到重视。一种异二聚吲哚生物碱，haplophytine具有特别复杂的十个环，六个立体中心（其中五个是四元的）和一个高度密集的碳碳键连接分子的两个不同的一半。四环左侧结构域具有独特的桥连酮结构，而右侧结构域由天然存在的盾籽植物生物碱aspidophytine组成（2，方案1b）。在Cava、Yates和Zacharias的小组进行了广泛的化学降解、光谱和X射线晶体学研究，包括鉴定二氢溴酸盐衍生物3（方案1a）之后，在其分离之后的大约21年，才完全了解了haplophytine的分子结构。如图所示，该化合物是通过涉及缩醛胺C N键的1，2-移位的左手结构域的独特酸介导的骨架重排形成的。然而，在碱性条件下，该过程可以逆转，例如通过互补的半频哪醇型机制返回haplophytine。作为
Despite the many impressive accomplishments in the field of total synthesis in recent years, a number of natural products have proven stubbornly resistant to its advances. Among them is haplophytine (1, Scheme 1a), which has only very recently succumbed to synthesis following the elegant work of Fukuyama, Tokuyama and co-workers. Haplophytine was first isolated by Snyder and co-workers in 1952, and identified as the principle bioactive component of the wild flower Haplophyton cimicidum, valued for centuries by the Aztecs and subsequent settlers of Central America for its insecticidal properties. A heterodimeric indole alkaloid, haplophytine features a particularly complex polycyclic array of ten rings, six stereocenters (five of which are quaternary) and a highly congested carbon carbon bond adjoining the two distinct halves of the molecule. The tetracyclic left-hand domain features a unique bridged ketone structure, while the righthand domain consists of the naturally occurring aspidosperma alkaloid, aspidophytine (2, Scheme 1b). A complete appreciation of haplophytine s molecular structure was only reached some 21 years subsequent to its isolation, following extensive chemical degradation, spectroscopic, and X-ray crystallographic studies from the groups of Cava, Yates, and Zacharias, which included identification of the dihydrobromide derivative 3 (Scheme 1a). As depicted, this compound is formed through a unique acid-mediated skeletal rearrangement of the left-hand domain involving the 1,2-shift of an aminal C N bond. Under basic conditions, however, this process can be reversed such as to return haplophytine through a complementary semi-pinacol type mechanism. As