Collective Synthesis of Aplysiatoxin/Oscillatoxin Analogues by a Bioinspired Strategy
Collective Synthesis of Aplysiatoxin/Oscillatoxin Analogues by a Bioinspired Strategy
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DOI：
10.1021/acs.joc.2c02204
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发表时间：
2022-11-04
影响因子：
3.6
通讯作者：
Nishikawa，Toshio
中科院分区：
文献类型：
--
作者：
Hada，Kohei;Araki，Yusuke;Nishikawa，Toshio
近年来，由于发现了许多新的类似物，其中一些具有有趣的生物活性，海洋蓝藻天然产物阿朴氏毒素（ATX）和阿朴氏毒素（OTX）重新引起人们的兴趣。我们试图开发这些天然产物的集体合成，假设ATX可以作为共同的生物合成前体。在这里，我们揭示了ATX的核心结构具有独特的多重反应性，根据所使用的具体条件，可以获得五种类似物的不同环结构。在此基础上，以ATX的主要片段为中间体，经几步反应合成了五种类似物neo-deBr-ATX-B、OTX-H、OTX-D、neo-deBr-ATX-H和OTX-I的O-Me衍生物。这些合成研究还使我们修正了neo-deBr-ATX-B和OTX-H的已阐明结构中的相对构型，并从同一中间体获得非天然的8元和12元内酯。
Interest in the marine cyanobacteria natural products aplysiatoxin (ATX) and oscillatoxin (OTX) has been renewed recently due to the discovery of many new analogues, some exhibiting intriguing biological activities. We sought to develop a collective synthesis of these natural products, hypothesizing that ATX could serve as a common biosynthetic precursor. Herein, we reveal that the core structure of ATX has unique multiple reactivities giving access to the distinct ring structures of five of the analogues, depending upon the specific conditions used. Based on these findings, syntheses of theO-Me derivative of five analogues neo-deBr-ATX-B, OTX-H, OTX-D, neo-deBr-ATX-H, and OTX-I were achieved from the main fragment of ATX as a common intermediate in a few steps. These synthetic studies also led us to revise the relative configuration in the elucidated structures of neo-deBr-ATX-B and OTX-H, and obtain unnatural 8- and 12-membered lactones from the same intermediate.