Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany.
J Org Chem. 2021 Jun 4;86(11):7537-7551. doi: 10.1021/acs.joc.1c00580. Epub 2021 May 20.
The AB ring systems of the clifednamide family, polycyclic tetramate macrolactames (PoTeMs), were prepared by a new, convergent approach employing an intramolecular Diels-Alder (IMDA) reaction. Key steps comprise an organocatalytic Michael addition (>90% enantiomeric excess (ee)), a Mukaiyama aldol reaction for the convergent installation of a diene moiety, and a telescoped hydrozirconation/cross-coupling grafting an enone. The following IMDA furnished a highly functionalized hydrindane (diastereomeric ratio (dr) = 91:1) with the same configuration as the clifednamide scaffold. Advantages of this route are only one required protecting group, 13% overall yield over 9 steps (reduced from previously 17 steps/1.3% overall), and the potential access to the key intermediates in the clifednamide biosynthesis.
克莱菲丹酰胺家族的 AB 环系统，多环四肽大环内酯（PoTeMs），可通过一种新的、收敛的方法制备，该方法采用分子内 Diels-Alder（IMDA）反应。关键步骤包括：一个有机催化的迈克尔加成（>90%对映体过量（ee））、一个 Mukaiyama 羟醛缩合反应，用于二烯部分的收敛安装，以及一个缩合的锆氢化/交叉偶联接枝烯酮。以下的 IMDA 提供了一个高度官能化的氢化茚满（非对映异构体比例（dr）=91:1），与克莱菲丹酰胺支架具有相同的构型。该路线的优点是仅需一个保护基团，总收率为 9 步的 13%（从之前的 17 步/总收率 1.3%减少），并且有可能获得克莱菲丹酰胺生物合成中的关键中间体。
