A synthetic study of atropurpuran: construction of a pentacyclic framework by an intramolecular reverse-electron-demand Diels-Alder reaction.
A synthetic study of atropurpuran: construction of a pentacyclic framework by an intramolecular reverse-electron-demand Diels-Alder reaction.
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DOI：
10.1002/anie.201103950
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发表时间：
2011-09
影响因子：
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通讯作者：
Takahiro Suzuki;Aya Sasaki;Naoki Egashira;Susumu Kobayashi
中科院分区：
文献类型：
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作者：
Takahiro Suzuki;Aya Sasaki;Naoki Egashira;Susumu Kobayashi
乌头是一种开花植物属，能产生多种具有药用价值的毒药和化合物。这些化合物的令人着迷的生物活性来自于C19和C20二萜生物碱，如乌头碱、猪鬃碱、猪鬃碱和猪鬃碱然而，从乌头属植物中分离到非生物碱二萜的报道很少2009年，Wang等报道了从乌头（Aconitum hemsleyanum var. atropurpureum, Scheme1）中分离到结构独特的非生物碱二萜atropurpuran(1)[3]。atropurpuran的结构具有前所未有的笼状骨架，由五个六元环（A， B， C， D和E环）组成。有趣的是，B、C、D和E环构成了四环环[5.3]。3.04, 9。[04,12]-三烷烃骨架，其中包括两个双环[2.2]。2]辛烷值单位。这种不寻常的笼状结构基序仅在从乌头根中分离出的几种二萜生物碱中发现，即arcutin(2)、arcutinine(3)和arcutinine (4)化合物2-4与阿托特紫癜密切相关，不同之处在于atC-19的取代（即通过形成1-吡咯环）和c - 1,10双键的羟基化。尽管四环环具有有趣的生物合成和结构特性[5.3]。3.04, 9。[04,12]三烷烃骨架，以前没有报道描述合成该化合物的努力。因此，在我们对1的综合调查开始时，我们试图建立一种构建四环骨架的方法。在这里，我们报告了第一个进入四环[5.3]。3.04, 9。[04,12]通过分子内Diels-Alder反应得到三烷烃骨架和1的五环碳骨架。
Aconitum is a genus of flowering plants that produce a variety of poisons and compounds of medicinal importance. The fascinating bioactivities of these compounds arise from C19 and C20 diterpene alkaloids, such as aconitine, hetisine, atisine, and kobusine.[1] Isolation of non-alkaloidal diterpenes from the genus Aconitum, however, has rarely been reported.[2] In 2009, Wang and co-workers reported the isolation of the structurally unique non-alkaloidal diterpene atropurpuran (1)[3] from Aconitum hemsleyanum var. atropurpureum (Scheme1). The structure of atropurpuran features an unprecedented cage-like skeleton that consists of five sixmembered rings (A, B, C, D, and E rings). Intriguingly, the B, C, D, and E rings constitute the tetracyclo [5.3. 3.04, 9. 04, 12]-tridecane skeleton, which includes two bicyclo [2.2. 2] octane units. This unusual cage-like structural motif is only found in a few members of the diterpene alkaloids, namely arcutin (2), arcutinine (3), and arcutinidine (4), which were isolated from the roots of Aconitum arcuatum.[4] Compounds 2–4 are closely related to atropurpuran and only differ in the substitution atC-19 (ie, by forming a 1-pyrroline ring) and the hydroxylation of the C-1, 10 double bond. Despite the intriguing biosynthetic and structural properties of the tetracyclo [5.3. 3.04, 9. 04, 12] tridecane skeleton, there are no previous reports that describe efforts to synthesize this compound. Consequently, at the outset of our synthetic investigation on 1, we attempted to establish a methodology for the construction of the tetracyclic skeleton. Herein, we report the first entry to a tetracyclo [5.3. 3.04, 9. 04, 12] tridecane skeleton and the pentacyclic carbon framework of 1 through an intramolecular Diels–Alder reaction of masked orthobenzoquinone (MOB).