Synthesis of Biologically Active Alkaloids and Lead Compounds for Drug Development

1.以Grubbs卡宾化钌催化剂与三甲基硅氧基乙烯醚为原料，研制了一种新型异构化和环异构化催化剂。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，我们已经成功地合成了从威尔士洋葱的根中分离出来的fistulosin的假定结构，并报道了它具有抗真菌活性。从2-氨基苯乙烯入手，制备了化合物，并用光谱方法对其进行了表征。然而，光谱数据与报道的fistulosin不一致。我们研究了Kopsia生物碱lapidilecam和lundrine B的全合成方法，虽然lpidilecam的生物活性尚未见报道，但lundrine B具有很强的抗癌活性。在本课题组研究的基础上，采用Heck型环化-烯烃异构化方法合成了中心核。全合成的进一步研究将继续进行。开发了呋喃-镁离子环化反应。这一反应的应用已经在从冲绳收集的海绵中分离的一种海洋生物碱中adomarin A的首次全合成中得到了报道。进一步的研究进一步阐明了该反应的范围和局限性，我们发现该反应可以应用于其他底物。介绍了一种新的合成曼扎胺A的生物遗传合成中间体药物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.