Intramolecular Schmidt Rearrangement Reaction And Its Application In The Total Syntheses Of Alkaloids

Intramolecular Schmidt reaction is one of the effective methods to build complex aza-polycyclic skeleton. and its application in the total syntheses of alkaloids has been an important research project. Based on this backgroud. an efficient synthesis of the immunosuppressive alkaloid (-)-FR901483was achieved by using the intramolecular Schmidt reaction as the key step. In addition, this interesting reaction was used for constructing the key skeleton of stemona alkaloids.Chapter1reviewed the history and research progress of the intramolecular Schmidt reaction. Also. the splendid applications of this reaction or related cascade reaction in the total synthesis of alkaloids were summarized.Chapter2elaborated on the total synthesis of the immunosuppressive alkaloid (-)-FR901483. This work was completed in3.5%overall yield and16steps from commercially available1.4-dioxaspiro[4.5]decan-8-one. In study of intramolecular Schmidt reaction. chlorosulfonic acid was developed as the promoter for the first time due to the complexity of the substrate. Necessity of this strong acid and the reason of the unsuccessful reaction with the Lewis acids as the promoter were presented after analyzing X-ray crystal structures of the substrates.Chapter3described the synthetic attempts of stemona alkaloids-Neostmonie and Neostemodiol by exploring initially the intramolecular Schmidt reaction. The key skeleton of target alkaloids has been synthesized and the follow-up work is in progress. This unfinished work deepened our understanding of the intramolecular Schmidt reaction and reaction properties of the stemona alkaloids’ skeleton.