Synthesis of Biologically Active Alkaloids and Lead Compounds for Drug Development

1.以三甲基硅氧基乙烯基醚为原料，合成了一种新型的三甲基硅氧基乙烯醚异构化环异构化催化剂。利用该催化剂，我们开发了一种合成吲哚和3-亚甲基吲哚的新方法。作为该反应的一个应用，我们成功地合成了从洋葱根或大葱中分离出来的具有抗真菌活性的假想结构。以2-氨基苯乙烯为起始原料，制备了化合物，并用光谱手段进行了表征。2.我们研究了Kopsia生物碱Lapidilectam和Lapdrine B的全合成。虽然Lapidilectam的生物活性尚未见报道，但Lapdrine B具有很强的抗癌活性。以本课题组开发的策略为基础，采用Heck环化反应和烯烃异构化反应合成了中心核。全合成还需进一步研究。3.对呋喃亚胺正离子环化反应进行了研究。该反应已被首次用于从冲绳采集的海绵中分离出的海洋生物碱Nakadomarin A的全合成中。进一步的研究进一步澄清了该反应的范围和局限性，我们发现该反应也可以应用于其他底物。开发了一种新的合成曼珠明A的生物合成中间体淫羊藿苷A的方法。

1.A new isomerization and cycloisomerization catalyst was developed by the reaction of Grubbs ruthenium carbine catalyst and trimethylsilyloxyvinylether. Using the catalyst, we developed a new method for the synthesis of indoles and 3-methyleneindolines. As an application of this reaction, we have succeeded in the synthesis of the putative structure of fistulosin which was isolated from the root or the Welsh onion and reported to have antifungal activity. Starting from 2-aminostylene, we have prepared the compounds and characterized by spectral means. However, the spectral data was not agree with those reported for fistulosin.2.We have studied a total synthesis of Kopsia alkaloid lapidilectam and lundrine B. Although the biological activity of lapidilectam has not been reported, lundrine B has strong activity of anti-cancer activity. Based on the strategy developed by our group, central core was synthesized using Heck type cyclization with isomerization of olefin. Further study will be continued for the total synthesis.3.Furan-iminium cation cyclization was developed. An application of this reaction has already been reported in the first total synthesis of nakadomarin A, a marine alkaloid isolated from sponge collected at Okinawa. Further study has been continued to clarify the scope and limitation of this reaction and we found that the reaction could be applied for other substrate. A new synthetic method for ircinal A, a biogenetical and synthetic intermediate for manzamine A, has been developed.