Cohen Frederick, Overman Larry E
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, 92697-2025, USA.
J Am Chem Soc. 2006 Mar 1;128(8):2604-8. doi: 10.1021/ja057433s.
Batzelladine F (1) was synthesized in enantioselective and stereoselective fashion in 15 steps (longest linear sequence) and 1.7% overall yield from two readily available enantioenriched beta-hydroxy esters, methyl (R)-3-hydroxydecanoate and methyl (R)-3-hydroxybutyrate. Tethered Biginelli condensations are used to assemble both tricyclic guanidine fragments, with the second tethered Biginelli condensation (14 + 16 --> 17) also being employed to join the guanidine fragments. Three diastereomers of batzelladine F, 2-4, were prepared also. A combination of HPLC, optical rotation and CD spectroscopy was employed to distinguish stereoisomers 1-4, proving that 1 is the correct structure of the hexacyclic marine alkaloid batzelladine F.
巴泽拉定F(1)以对映选择性和立体选择性方式从两种易于获得的对映体富集的β-羟基酯,(R)-3-羟基癸酸甲酯和(R)-3-羟基丁酸甲酯经15步(最长线性序列)合成,总产率为1.7%。通过连接的Biginelli缩合反应组装两个三环胍片段,第二个连接的Biginelli缩合反应(14 + 16 → 17)也用于连接胍片段。还制备了巴泽拉定F的三种非对映异构体,2 - 4。采用高效液相色谱、旋光和圆二色光谱相结合的方法区分立体异构体1 - 4,证明1是六环海洋生物碱巴泽拉定F的正确结构。