(+)-Mannolide B possesses an intriguing and complex 5/7/5/6/6/6-fused hexacyclic scaffold including two bridged-lactone moieties and nine contiguous stereocenters, and thus represents a formidable challenge for total synthesis. Herein, the evolution of a successful strategy for the synthesis of mannolide B is described. The 7/5 ring system of the 7/5/6/6 tetracyclic carbon skeleton was efficiently constructed by a ring-closing metathesis starting from commercially available (−)-methyl jasmonate. Attempts to access the 6/6 ring system were unexpectedly challenging. Initially, an intramolecular Diels–Alder reaction was designed; however, the desired cyclization precursor could not be obtained. Furthermore, a radical cascade cyclization was investigated and produced only one six-membered ring with poor stereoselectivity at C5. Finally, the 6/6 ring system was successfully generated through a Pauson–Khand reaction, followed by a highly regioselective Büchner–Curtius–Schlotterbeck reaction, enabling us to achieve the first total synthesis of (+)-mannolide B in 24 steps.

中文翻译：

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（+）-甘露内酯 B 的完全合成


（+）-甘露内酯 B 具有一个有趣且复杂的 5/7/5/6/6/6 熔合六环支架，包括两个桥式内酯部分和九个连续的立体中心，因此代表了全合成的巨大挑战。在此，描述了合成甘露内酯 B 的成功策略的演变。7/5/6/6 四环碳骨架的 7/5 环系统是通过从市售 （-）-甲基茉莉酸酯开始的闭环复分解有效地构建的。尝试访问 6/6 环系统出乎意料地具有挑战性。最初，设计了分子内 Diels-Alder 反应;然而，无法获得所需的环化前体。此外，研究了自由基级联环化，仅在 C5 处产生一个立体选择性较差的六元环。最后，通过 Pauson-Khand 反应成功生成 6/6 环系统，然后是高度区域选择性的 Büchner-Curtius-Schlotterbeck 反应，使我们能够通过 24 个步骤实现 （+）-甘露内酯 B 的首次全合成。