Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13575-13581. doi: 10.1002/anie.201808937. Epub 2018 Sep 17.
The marine macrolide chagosensine is the only natural product known to date that embodies a Z,Z-configured chloro-1,3-diene unit. This distinguishing substructure was prepared by a sequence of palladium-catalyzed 1,2-distannation of an alkyne precursor, regioselective Stille cross-coupling at the terminus of the resulting bisstannyl alkene with an elaborated alkenyl iodide, followed by chloro-destannation of the remaining internal site. The preparation of the required substrates centered on cobalt-catalyzed oxidative cyclization reactions of hydroxylated olefin precursors, which allowed the 2,5-trans-disubstituted tetrahydrofuran rings, embedded into each building block, to be formed with excellent selectivity. The highly strained macrolactone could ultimately be closed under forcing Yamaguchi conditions. Comparison of the spectral data of the synthetic sample with those of authentic chagosensine methyl ester confirmed that the structure of this intriguing compound has been mis-assigned by the isolation team.
海洋大环内酯类 chagosensine 是目前为止唯一已知的含有 Z,Z 构型氯-1,3-二烯单元的天然产物。这个独特的结构是通过一系列钯催化的炔烃前体的 1,2-二锡化反应、在生成的双锡烯的末端与经过精心设计的烯基碘化物进行区域选择性的 Stille 交叉偶联、以及剩余内部位点的氯脱锡反应来制备的。所需底物的制备集中在钴催化的羟基化烯烃前体的氧化环化反应上，这使得每个构建块中嵌入的 2,5-反式二取代四氢呋喃环能够以极好的选择性形成。在强 Yamaguchi 条件下，最终可以闭环形成高度应变的大环内酯。合成样品的光谱数据与天然 chagosensine 甲酯的光谱数据进行比较，证实了该分离团队对这种有趣化合物的结构进行了错误的归属。
