Fettes Alec, Carreira Erick M
Laboratorium für Organische Chemie, ETH Hönggerberg, Wolfgang Pauli Strasse 10, CH-8093 Zürich, Switzerland.
J Org Chem. 2003 Nov 28;68(24):9274-83. doi: 10.1021/jo034964v.
The total synthesis of the biologically active marine natural product leucascandrolide A is reported. A convergent strategy is employed, allowing for the rapid assembly of the macrolide moiety. Key steps of our approach include the diastereoselective addition of a zinc alkynilide to (R)-isopropylidene glyceraldehyde, the enantioselective copper(I) fluoride catalyzed aldol addition of a TMS-dienolate to crotonaldehyde, and the formation of a 2,6-trans-substituted tetrahydropyran by selenium-mediated intramolecular cyclization. Moreover, dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role. An improved route to a key intermediate of our synthesis is documented.
报道了具有生物活性的海洋天然产物亮叶海松素A的全合成。采用了汇聚策略，能够快速组装大环内酯部分。我们方法的关键步骤包括将锌炔基化物非对映选择性地加成到(R)-异亚丙基甘油醛上、铜(I)氟化物催化的TMS-烯醇化物与巴豆醛的对映选择性羟醛加成反应，以及通过硒介导的分子内环化形成2,6-反式取代的四氢吡喃。此外，在大环内酯化反应中观察到的显著溶剂效应表明氢键效应起着关键作用。记录了一条改进的合成关键中间体的路线。
