The true structures of the vannusals, part 1: Initial forays into suspected structures and intelligence gathering.
The true structures of the vannusals, part 1: Initial forays into suspected structures and intelligence gathering.
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DOI：
10.1002/anie.200902028
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发表时间：
2009
影响因子：
16.6
通讯作者：
Ortiz, Adrian
中科院分区：
文献类型：
--
作者：
Nicolaou, K. C.;Zhang, Hongjun;Ortiz, Adrian
从热带间质纤毛虫 Euplotes vannus 菌株 Si121 和 BUN3 中分离出来的 vannusal A 和 B 分别被指定为结构 1 和 2（图 1）。[1, 2] 这些新颖且具有挑战性的分子结构自 1999 年公开以来一直令科学家们着迷，直到 2008 年我们报道了 vannusal B 最初指定结构的首次全合成 (2) 和事实证明这是错误的。[3]由于天然产物的稀缺性及其前所未有的碳骨架，万努柳B的正确结构之谜变得更加复杂，因此将其解决方案的挑战留给了化学合成。在本次和接下来的通讯中，[4]我们报告了我们的研究，这些研究导致了该分子的几种可疑立体异构体的全合成，并通过其全合成最终阐明了其真实结构（及其兄弟姐妹，vannusal A）。基于全合成和核磁共振波谱之间的相互作用，了解 vannusal B 的真实结构的旅程是漫长而艰巨的。它变得紧急，并在完成其最初分配的结构（2）的全合成后立即启动。 [3]在下面的描述中，我们将揭示事件的逻辑演变，这些事件导致了有用情报的出现，从而最终解决了万努萨尔难题。因此，通过比较天然万努醛 B 和合成 2 的 NMR 光谱数据，很明显，最显着的差异位于分子的“东北”区域，特别是环 D 和 E 周围。强有力的 NMR 光谱证据（见图 2）表明立构中心 C26（w 耦合，JH26，15left= 1.6 Hz；NOE，H26/H27）和 C18（NOE， H25/H16）可能是正确的，因此将 C25 和 C21 作为开始我们的结构修改的最合乎逻辑的位置。这将我们的选择范围缩小到四种非对映体结构，其中一种（即 2 个）我们已经合成。 [3]从剩下的三个中，我们选择了 2 的 C21-epi 非对映异构体，结构 3（图 1），作为我们的下一个目标分子，基于一个微妙而有趣的观察：C21 处的构型反转将使 vannusalB 的“东北”结构域符合所提出的生物合成假设，该假设假设两个相同的单体单元（prevannusal，自然是
Isolated from the tropical interstitial ciliate Euplotes vannus strains Si121 and BUN3, vannusals A and B were assigned structures 1 and 2, respectively (Figure 1).[1, 2] These novel and challenging molecular architectures have fascinated scientists since their disclosure in 1999, and stood defiant to chemical synthesis until 2008, when we reported the first total synthesis of the originally assigned structure of vannusal B (2) and proved it to be wrong.[3] The puzzle of the correct structure of vannusal B was complicated by the scarcity of the natural product and its unprecedented carbon framework, thus leaving the challenge of its solution to chemical synthesis. In this and the following communication,[4] we report our investigations that led to the total synthesis of several suspected stereoisomers of this molecule and the eventual elucidation of its true structure (and that of its sibling, vannusal A) through its total synthesis. Based on the interplay between total synthesis and NMR spectroscopy, the journey to the true structure of vannusal B was long and arduous. It became urgent and was initiated immediately upon completion of the total synthesis of its originally assigned structure (2).[3] In the following description, we unravel the logical evolution of events that led to the emergence of useful intelligence that allowed the eventual solution of the vannusal conundrum. Thus, upon comparison of the NMR spectroscopic data of natural vannusal B and synthetic 2, it became apparent that the most striking differences were located in the “northeastern” region of the molecule, particularly around rings D and E. Strong NMR spectroscopic evidence (see Figure 2) indicated that stereocenters C26 (w-coupling, JH26, 15left= 1.6 Hz; NOE, H26/H27) and C18 (NOE, H25/H16) were likely to be correct, thus leaving C25 and C21 as the most logical positions to start our structural modifications. This narrowed our choice to four diastereomeric structures, one of which (ie 2) we had already synthesized.[3] From the remaining three, we selected the C21-epi diastereomer of 2, structure 3 (Figure 1), as our next target molecule based on a subtle and intriguing observation: inversion of the configuration at C21 would bring the “northeastern” domain of vannusalB in line with the proposed biosynthetic hypothesis that postulated dimerization of two identical monomeric units (prevannusal, which is naturally
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影响因子：
16.6
作者：
Nicolaou, K. C.;Zhang, Hongjun;Dagneau, Philippe
通讯作者：
Dagneau, Philippe
影响因子：
16.6
作者：
Nicolaou, K. C.;Ortiz, Adrian;Zhang, Hongjun
通讯作者：
Zhang, Hongjun
影响因子：
2.8
作者：
Guella, Graziano;Callone, Emanuela;Dini, Fernando
通讯作者：
Dini, Fernando
影响因子：
15
作者：
Shibuya, Masatoshi;Tomizawa, Masaki;Iwabuchi, Yoshiharu
通讯作者：
Iwabuchi, Yoshiharu
DOI：
10.1002/(sici)1521-3773(19990419)38:8
发表时间：
1999-01-01
影响因子：
16.6
作者：
Guella, G;Dini, F;Pietra, F
通讯作者：
Pietra, F