Department of Chemistry, Centre of Novel Functional Molecules, Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.
Chemistry. 2011 May 16;17(21):5874-80. doi: 10.1002/chem.201003309. Epub 2011 Apr 13.
The total synthesis of plakortide E (1a) is reported. A novel palladium-catalyzed approach towards 1,2-dioxolanes as well as an alternative substrate-controlled route leading exclusively to cis-highly substituted 1,2-dioxolanes have been developed. A lipase-catalyzed kinetic resolution was employed to provide optically pure 1,2-dioxolane central cores. Coupling of the central cores and side chains was achieved by a modified Negishi reaction. All four isomeric structures of plakortide E methyl ester, namely, 26a-d were synthesized. One of the structures, 26d, was shown to be identical with the natural plakortide E methyl ester on the basis of (1)H, (13)C NMR spectra and specific rotation comparisons. With the plakortide E methyl ester (4S,6R,10R)-(-)-cis-26d and its other three isomers in hand, we successfully converted them into (3S,4S,6R,10R)-plakortone B (2a), and its isomers ent-2a, 2b and ent-2b via an intramolecular oxa-Michael addition/lactonization cascade reaction. Finally, saponification converted 1,2-dioxolane 26d into plakortide E (1a) whose absolute configuration (4S,6R,10R) was confirmed by comparison of spectral and physical data with those reported.
报道了 plakortide E（1a）的全合成。开发了一种新型钯催化的 1,2-二氧戊环合成方法以及一种替代性的底物控制途径，该途径可专一地得到顺式高取代的 1,2-二氧戊环。采用脂肪酶催化动力学拆分，提供了光学纯的 1,2-二氧戊环中心核。通过改良的 Negishi 反应，将中心核和侧链偶联。合成了 plakortide E 甲酯的四个异构体，即 26a-d。其中一个结构，26d，基于（1）H、（13）C NMR 谱和比旋光度比较，被证明与天然 plakortide E 甲酯相同。在手性 plakortide E 甲酯（4S,6R,10R）-（-）-cis-26d 及其另外三个异构体的基础上，我们成功地将它们转化为（3S,4S,6R,10R）-plakortone B（2a）及其异构体 ent-2a、2b 和 ent-2b，通过分子内氧杂-Michael 加成/内酯化级联反应。最后，皂化将 1,2-二氧戊环 26d 转化为 plakortide E（1a），其绝对构型（4S,6R,10R）通过与文献报道的光谱和物理数据的比较得到证实。
