Development of New Synthetic Reactions and their Application to the Synthesis of Biologically Active Compounds

在BF_3·OEt_2的作用下，碳链末端带有醛基的γ-氧代烯丙基锡的分子内环化反应以立体控制的方式进行，得到了高非对映选择性的七元β-羟基环醚。应用该方法合成了6-7-7-6环系统作为短尾孢毒素B的模型化合物。在研究过程中，我们发现Bu_4 NF-TiCl_4催化的（Z）-owega-锡醛环化反应生成顺式环醚，而（E）-异构体生成反式环醚。为了解释这种立体化学结果，提出了推拉机制。采用烯丙基锡法，尝试全合成半短吻蝮蛇毒素B，现已完成了其必需环骨架6-6-7-7体系的立体控制合成。

The BF_3.OEt_2 mediated intramolecular cyclization of the gamma-oxo-substituted allylic tin having an aldehyde group at the terminus of the carbon chain proceeds in a stereocontrolled manner to give the seven membered beta-hydroxy cyclic ether with high diastereoselectivity. This method was applied for the synthesis of a 6-7-7-6 ring system as a model of brevetoxin B. On the way of this investigation we discovered that Bronsted acid catalyzed of Bu_4NF-TiCl_4 mediated cyclization of (Z)-owega-stannyl aldehyde gives syn cyclic ether, whereas (E)-isomer affords anti cyclic ether. To explain this stereochemical outcome, a push-pull mechanism was proposed. By using the allylic tin method, total synthesis of hemibrevetoxin B was attempted, and now have completed the stereocontrolled synthesis of the essential ring framework,6-6-7-7 system.