Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate Prorocentrum sp, whose structure is characterized by functionalized 5- and 6-membered ether rings embedded in the macrolactone and an all cis-tetraene side chain. Here, we report the synthesis of the macrolactone core of ent-formosalide A. Our approach is highlighted by the Au-mediated 6-exo-dig cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner. Control experiments demonstrated that the acyclic protecting group of the C9,C10-diol was crucial for the desired 6-exo-dig cyclization. Theoretical studies were performed focusing on structural component analysis, which suggested that the C8–C9–C10-C11 dihedral angle induced by the protecting group controlled the regioselectivity. An additional 6 steps including Shiina macrolactone formation from the 6-membered ether ring completed the synthesis of the macrolactone core of ent-formosalide A.

中文翻译：

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区域选择性醚环化合成对映福莫内酯 A 的大环内酯核心

Formosalide A 是一种从甲藻原甲藻中分离出来的细胞毒性大环内酯，其结构特征是嵌入大环内酯中的功能化 5 元和 6 元醚环以及全顺式四烯侧链。在这里，我们报告了ent -formosalide A的大环内酯核心的合成。我们的方法以 Au 介导的 6- exo - dig环化来合成 6 元醚环为重点，该环化以高度区域选择性的方式进行。对照实验表明，C9,C10-二醇的无环保护基团对于所需的6- exo - dig环化至关重要。理论研究侧重于结构成分分析，表明保护基诱导的 C8-C9-C10-C11 二面角控制了区域选择性。另外 6 个步骤，包括从 6 元醚环形成椎名大内酯，完成了ent -formosalide A的大内酯核心的合成。