A New Method To Construct 2, 3, 6-trisubstituted Piperidines Using Enantiopure

In the modern organic synthesis, it is an important method to synthesize optical pure compounds starting from the appropriate chiral pools. As a frequently used chiral pool, amino acids have been used extensively in the syntheses of nitrogen-containing compounds for a few decades. However, very limited reports have appeared regarding synthesis from enantiopure (-amino acids mainly because it was rather difficult to obtain enantiopure (-amino acids before. Recently because some easy ways of getting optical pure (-amino acids have been found, the application of them in organic synthesis has become more and more popular.In this thesis, we developed a new method to construct 2, 3, 6-trisubstituted piperidines using enantiopure (-amino acid derivatives as the starting material and applied them to the synthesis of some piperidine alkaloids which showed interesting physiological activities.In the first chapter of this thesis, we prepared the desired (-amino acid ester starting from 1-tridecanol and converted it to the corresponding ?-amino alcohol via LAH reduction and hydrogenolysis. Condensation of this (-amino alcohol and acyl acetone afforded an enamine, which was subjected to an intramolecular cyclization to provide a cyclic enamine. After diastereoselective hydrogenation a 2, 3, 6-trisubstituted piperidine was obtained, which was transformed into (-)-deoxocassine using the Bayer-Villager oxidation as the key step. In the second chapter of this thesis, we prepared an enantiopure ?-amino alcohol by the same method as mentioned above. This ?-amino alcohol was added to THP-protected 5-hydroxy-3-pentyn-2-one to give an enamine. After doing the same transformations as mentioned in the chapter one except for an isomerization step, we obtained (-)-deoxoprosophylline in 7.0% total yield.In the third chapter, we used 1,10-decanedioic acid and 1,7-heptandiol as the starting materials, and the similar strategy mentioned above, to finish total synthesis of (-)-irnigaine and (+)-azimic acid in 8.4% and 3.0% total yield, respectively.