Schuppan Julia, Wehlan Hermut, Keiper Sonja, Koert Ulrich
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Chemistry. 2006 Sep 25;12(28):7364-77. doi: 10.1002/chem.200600461.
An efficient stereocontrolled synthesis of apoptolidinone A, the aglycone of apoptolidin A is described. The synthetic strategy relies on a cross coupling between C11/C12 of a northern half (C1-C11) and a southern part (C12-C28) followed by a ring-size selective macrolactonization. Key steps for the introduction of the southern half stereocenters are a stereoselective aldol reaction, a substrate controlled dihydroxylation and a chelation-controlled Grignard/aldehyde addition. The conjugated triene of the northern half was built up successively by E-selective Wittig reactions. L-Malic acid was chosen as the chiral pool source for the C8/C9 stereocenters. The final cleavage of the silyl ethers and the conversion of the C21 methyl ketal into the hemiketal was achieved by HF.pyridine.
描述了一种高效的立体控制合成凋亡素 A 的苷元凋亡素酮 A 的方法。合成策略依赖于北半部分（C1-C11）的 C11/C12 与南半部分（C12-C28）之间的交叉偶联，随后进行环大小选择性大环内酯化。引入南半部分立体中心的关键步骤是立体选择性羟醛反应、底物控制的二羟基化反应以及螯合控制的格氏试剂/醛加成反应。北半部分的共轭三烯通过 E 选择性维蒂希反应依次构建。选择 L-苹果酸作为 C8/C9 立体中心的手性池来源。通过 HF·吡啶实现了硅醚的最终裂解以及 C21 甲基缩酮向半缩酮的转化。
