北京大学贾彦兴研究团队取得一项新突破。他们成功实现了(+)-甘露糖醇内酯B的全合成。相关论文发表在2024年12月17日出版的《美国化学会杂志》上。

(+)-甘露糖醇内酯B具有一个有趣而复杂的5/7/5/6/6/6-六环并环的的框架，包括两个桥式内酯基团和九个连续的立体中心，这对全合成来说是一个巨大的挑战。本文描述了一种成功合成(+)-甘露糖醇内酯B的策略演变。

研究人员以市售的(−)-methyl jasmonate为原料通过关环复分解，高效构建了7/5/6/6四环骨架的7/5环体系。合成6/6环系统的尝试出乎意料地具有挑战性。最初，研究人员设计了分子内Diels-Alder反应；然而，无法得到所需的环化前体。

后来，研究人员研究了自由基级联环化，只产生了一个C5位置立体选择性差的六元环。最后，研究人员通过Pathemon-Khand反应成功生成了6/6环体系，随后进行了高度区域选择性的Büchner–Curtius–Schlotterbeck反应，使他们在24步内首次实现了(+)-甘露糖醇内酯B的全合成。

附：英文原文

Title: Total Synthesis of (+)-Mannolide B

Author: Peng Chen, Lijun Chen, Hongpeng Lin, Yanxing Jia

Issue&Volume: December 17, 2024

Abstract: (+)-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.

DOI: 10.1021/jacs.4c12767

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c12767