Wehlan Hermut, Dauber Mario, Fernaud M Teresa Mujica, Schuppan Julia, Keiper Sonja, Mahrwald Rainer, Garcia M-Elisa Juarez, Koert Ulrich
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Chemistry. 2006 Sep 25;12(28):7378-97. doi: 10.1002/chem.200600462.
The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11-C12 (cross-coupling) and C19O-C1 (macrocyclization). The cis-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue. Auxiliary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross-coupling of the glycosylated northern half with the glycosylated southern half was achieved with CuI-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.
描述了采用早期糖基化策略对凋亡素A进行全合成。在C11 - C12（交叉偶联）和C19O - C1（大环化）之间进行了策略性切断。通过在L - 葡萄糖残基的O2/O3处使用新的SIBA保护基实现了C9 - OH处的顺式选择性糖基化。在2 - 脱氧糖的2 - 位引入辅助取代基以选择性地形成C27二糖的糖苷键。用碘化亚铜 - 噻吩羧酸盐实现了糖基化的北半部分与糖基化的南半部分的交叉偶联。三羟基羧酸的大环化选择性地生成了20元大环内酯。H2SiF6适用于硅醚的最终脱保护以及将C21甲基缩酮转化为半缩酮。一些糖变体的合成证明了该方法的合成灵活性。
