Synthesis of Biologically Active Alkaloids and Lead Compounds for Drug Development

用于药物开发的生物活性生物碱和先导化合物的合成

基本信息

批准号：
16390003
负责人：
NISHIDA Atsushi
金额：
$ 8.32万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

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.

1.通过格鲁布斯钌卡宾催化剂与三甲基硅氧基乙烯基醚反应，开发出一种新型异构化和环化异构化催化剂。利用该催化剂，我们开发了一种合成吲哚和3-亚甲基二氢吲哚的新方法。作为该反应的应用，我们成功合成了从根或大葱中分离出来的瘘管素的推定结构，并据报道具有抗真菌活性。从2-氨基苯乙烯开始，我们制备了化合物并通过光谱手段进行了表征。但光谱数据与fistulosin报道的不一致。2.我们研究了Kopsia生物碱lapidilectam和lundrine B的全合成。虽然lapidilectam的生物活性尚未见报道，但lundrine B具有很强的抗癌活性。活动。根据我们课题组开发的策略，采用Heck型环化和烯烃异构化合成了中心核。全合成将继续进一步研究。3.开发了呋喃-亚胺阳离子环化法。该反应的应用已在 nakadomarin A 的首次全合成中得到报道，nakadomarin A 是一种从冲绳收集的海绵中分离出来的海洋生物碱。进一步的研究已继续阐明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。开发了一种新的合成方法ircinal A，一种曼扎明A的生物合成中间体。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of Synthetic Sphingosine-1-phoshate analogs on Arachidonic Acid Metabolism and Cell Death

合成 1-磷酸鞘氨醇类似物对花生四烯酸代谢和细胞死亡的影响

DOI：
发表时间：
2004
期刊：
Biochemical Pharmacology Vol.68
影响因子：
0
作者：
Hiroyuki Nakamura;Yuko Takashiro;Tetsuya Hirabayashi;Syunji Horie;Yuuki Koide;Atsushi Nishida;Toshihiko Murayama
通讯作者：
Toshihiko Murayama

A Facile Synthesis of Vicinal Diamines Promoted by Low-valent Niobium : Preparation of Chiral Octahydrobisisoquinolines and Their Application to Catalytic Asymmetric Synthesis

低价铌促进的连位二胺的简易合成：手性八氢双异喹啉的制备及其在催化不对称合成中的应用