Total Synthesis of Clavilactones
Total Synthesis of Clavilactones
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克拉维拉内酯的全合成
DOI：
10.1021/acs.joc.7b03268
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Kin-ichi Tadano
中科院分区：
文献类型：
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作者：
Ken-ichi Takao;Kento Mori;Kenya Kasuga;Ryuki Nanamiya;Ayumi Namba;Yuuki Fukushima;Ryuichi Nemoto;Takuma Mogi;Hiroyuki Yasui;Akihiro Ogura;Keisuke Yoshida;Kin-ichi Tadano
克拉维拉酮A、B和D是从棍棒真菌培养物中分离出来的表皮生长因子受体酪氨酸激酶抑制剂。在这里，我们报告了这些棒状内酯的全合成的全部细节。我们合成方法的一个关键特征是开环/闭环复分解策略，允许将环丁烯羧酸盐简洁地转化为γ-丁烯内酯。再结合钛/联苯醚催化的多取代苯甲醛的不对称炔化反应和含二烯的硅烷缩醛的开环歧化反应，合成了10元碳环，从而实现了天然对映体(+)-克拉维内酯A和(−)-克拉维内酯B的全合成。此外，通过合成两个新结构确定了克拉维内酯D的正确结构。这项研究导致了修正的(+)-克拉维内酯D的不对称合成。
Clavilactones A, B, and D are epidermal growth factor receptor tyrosine kinase inhibitors that were isolated from cultures of the fungusClitocybe clavipes. Here, we report full details of the total synthesis of these clavilactones. A key feature of our synthetic approach is a ring-opening/ring-closing metathesis strategy that allows the concise transformation of a cyclobutenecarboxylate into a γ-butenolide. Coupled with enantioselective Ti/BINOL-catalyzed alkynylation of a multisubstituted benzaldehyde and ring-closing metathesis of a diene-bearing silylene acetal to construct the 10-membered carbocycle, this strategy enabled the total synthesis of the natural enantiomers (+)-clavilactone A and (−)-clavilactone B. In addition, the correct structure of clavilactone D was determined by the synthesis of two newly proposed structures. This research resulted in the asymmetric synthesis of the revised (+)-clavilactone D.