Biomimetic Construction of a syn-2,7-Dimethyloxepane Ring via 7-Endo Cyclization.
Biomimetic Construction of a syn-2,7-Dimethyloxepane Ring via 7-Endo Cyclization.
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DOI：
10.1021/acs.joc.1c02600
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发表时间：
2021-12
期刊：
影响因子：
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通讯作者：
Takeo Sakai;Sae Mizuno;Akitaka Sone;Y. Hori;Wakana Yamazaki;Keisuke Takazawa;Y. Mori
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文献类型：
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作者：
Takeo Sakai;Sae Mizuno;Akitaka Sone;Y. Hori;Wakana Yamazaki;Keisuke Takazawa;Y. Mori
2，7-二甲基氧杂环己烷是一种在天然梯形多环醚(LSP)中观察到的独特结构，如加勒比海雪卡毒素、赤霉素B和灯盏花素-F等，具有很强的生物活性。因此，成功构建这个七元环是可取的，但它的环张力和它的两个甲基之间的1，3-排斥使这一过程变得困难。在这里，我们打破了鲍德温的规则，通过乙烯基环氧化合物的7-内环化反应制备了2，7-二甲基氧杂环己烷。这种仿生合成2，7-二甲基氧杂环己烷的方法还没有报道，然而，我们在顺式烯烃链条和未取代的乙烯基的帮助下实现了这一具有挑战性的环化反应。其中一个7-内环化产物还制备了裸盖霉素-B的无环片段，展示了该策略在构建生物活性LSP方面的潜在应用。
syn-2,7-Dimethyloxepane is a unique structure observed in natural ladder-shaped polycyclic ethers (LSPs), such as Caribbean ciguatoxins, gymnocin-B, and brevisulcenal-F that exhibit potent biological activities. Thus, the successful construction of this seven-membered ring is desirable, but its ring strain and the 1,3-repulsion between its two methyl groups makes this process difficult. Herein, we prepared syn-2,7-dimethyloxepanes via 7-endo cyclizations of vinyl epoxides that break Baldwin's rules. Such a biomimetic approach to syn-2,7-dimethyloxepanes has not yet been reported; however, we achieved this challenging cyclization with the aid of a cis-olefin tether and an unsubstituted vinyl group. The NO-ring fragment of gymnocin-B was also prepared from one of these 7-endo cyclized products, demonstrating the potential application of this strategy in constructing bioactive LSPs.