Synthesis and Structural Implication of the JKLMN-Ring Fragment of Caribbean Ciguatoxin C-CTX-1
Synthesis and Structural Implication of the JKLMN-Ring Fragment of Caribbean Ciguatoxin C-CTX-1
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DOI：
10.1021/acs.joc.0c03031
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发表时间：
2021-03-05
影响因子：
3.6
通讯作者：
Arai, Keisuke
中科院分区：
文献类型：
--
作者：
Sasaki, Makoto;Iwasaki, Kotaro;Arai, Keisuke
本文详细介绍了加勒比海和东北大西洋地区雪卡毒素C-CTX-1的JKLMN环片段的合成。合成的关键是通过[2，3]-Sigmatrotic重排来构建七元α-羟基外烯醇醚，通过氢原子转移还原烯烃偶联在七元M环上立体选择性地构筑有角度的四取代立体中心，KLMN环烯醇磷酸酯与高度堵塞的M环发生Suzuki-Miyaura偶联，以及硅胶介导的环氧化物开环形成J环。合成片段的核磁共振波谱数据与天然产物的核磁共振波谱数据的比较为C-CTX-1右手端N环的先前指定结构提供了支持。
Synthesis of the JKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the causative toxin of ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. Key to the synthesis are a [2,3]-sigmatropic rearrangement to construct a seven-membered alpha-hydroxy exo-enol ether, stereoselective construction of an angular tetrasubstituted stereogenic center on the seven-membered M-ring by a hydrogen atom transfer-based reductive olefin coupling, Suzuki-Miyaura coupling of the KLMN-ring enol phosphate with a highly congested M-ring, and silica gel-mediated epoxide ring opening to form the J-ring. Comparison of the nuclear magnetic resonance spectroscopic data for the synthesized fragment with those for the natural product provided support for the formerly assigned structure of the N-ring in the right-hand terminal of C-CTX-1.