Synthesis of Biologically Active Alkaloids and Lead Compounds for Drug Development

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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.