Concise Synthesis of Norrisolide
Concise Synthesis of Norrisolide
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DOI：
10.1002/ejoc.201200134
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发表时间：
2012-04-01
影响因子：
2.8
通讯作者：
Snapper, Marc L.
中科院分区：
文献类型：
--
作者：
Granger, Krista;Snapper, Marc L.
海洋天然产物去甲甘草酸酯的合成以收敛的方式进行，最长的线性序列为14步。通过将官能化烯丙基共轭加成到环戊烯酮中，然后用烯丙基亲电试剂立体选择性捕获由所得烯醇甲硅烷基醚产生的烯醇化物来制备分子的还原茚满部分。然后闭环复分解建立65环系统。同样，侧链的选择性制备的特征在于呋喃-2-酮的对映选择性环丙烷化，然后重排和氢化。两个主要片段通过Shapiro反应偶联，然后还原和烯化，完成天然产物的碳骨架。合成的最后步骤涉及调整侧链的氧化态。产生二氢茚核心和氧化侧链的新策略允许更简洁和有效地制备天然产物。
The marine natural product norrisolide has been synthesized in a convergent manner with a longest linear sequence of 14 steps. The hydrindane portion of the molecules is prepared through conjugate addition of a functionalized allyl group into cyclopentenone, followed by stereoselective trapping of the enolate generated from the resulting enol silyl ether with an allyl electrophile. Ring-closing metathesis then establishes the 65 ring system. Likewise, selective preparation of the side chain features an enantioselective cyclopropanation of furan-2-one, followed by rearrangement and hydrogenation. Coupling of the two major fragments through a Shapiro reaction, followed by reduction and olefination then completes the carbon framework of the natural product. The final steps of the synthesis involve adjustments to the oxidation state of the side chain. New strategies to generate both the hydrindane core and the oxidized side chain has allowed for the more concise and efficient preparation of the natural product.