Jiricek Jan, Blechert Siegfried
Institut für Chemie, Technische Universität Berlin, Strasse des 17 Juni 135, 10623 Berlin, Germany.
J Am Chem Soc. 2004 Mar 24;126(11):3534-8. doi: 10.1021/ja0399021.
Described is the first enantioselective synthesis of (-)-gilbertine (2), a member of the uleine-type family, and the determination of the absolute configuration of this natural product is reported. The key step employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and the construction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reaction to build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivative was achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol was used successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole (20). Furthermore, an unexpected behavior of this 2,3-disubstituted cyclohexanone derivative during an epimerization process was investigated, resulting in different chemical behavior of the enantiomers and the racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstrating the versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving (-)-gilbertine in 5.5% overall yield.
本文描述了乌灵碱型家族成员（-）-吉尔贝碱（2）的首次对映选择性合成，并报道了该天然产物绝对构型的确定。关键步骤采用阳离子串联反应一步形成四氢吡喃环和哌啶环并构建五环骨架。合成策略利用柴崎反应构建第一个手性中心。实现了3-取代环己酮衍生物的甲酰化反应，仅得到所需的区域异构体。Japp-Klingemann费歇尔吲哚反应方案成功用作构建所需四氢咔唑（20）的汇聚合成方法。此外，研究了该2,3-二取代环己酮衍生物在差向异构化过程中的意外行为，导致对映体和外消旋体具有不同的化学行为。通过阳离子串联反应实现了非对映体拆分，证明了该方法的通用性。值得注意的是，17步的合成序列易于实施，以5.5%的总收率得到（-）-吉尔贝碱。
