Total Synthesis Of Natural Quinolizidine And Indolizidine Alkaloid Compounds

For understanding the biological activity of alkaloids and developing the synthetic methods of them, the asymmetric synthesis of alkaloids has been received considerable attention by organic scientists.Chiral auxiliary synthesis is one of the efficient methods for the synthesis of alkaloids. Among which chiral amino-hydroxyl compounds had been fully studied in recent years. Chiral Betti base, an amino-hydroxyl compounds containing naphthalene and benzene structure, shows high potential in the chiral catalysis of piperidine alkaloids as an auxiliary reagent.In chapter 2, the reaction of Betti base compound with silyl-enol ethers of aceto-aromatic compounds was studied systematically. It proved to be an excellent method to construct the chiral 2-arylacyl-piperidine compounds in high stereoselectivity and efficiency. By using 2-arylacyl-piperidines as precursors, quinolizidine alkaloids (R)-Julandine and (R)-Cryptopleurine were synthesized.In chapter 3, retro-Mannich debenzylation of the Betti base residue under basic condition was studied and (R)-2-vinylpiperidine hydrochloride was easily obtained. Then we developed a novel method to convert it into the corresponding N-allyl aminopropanal oxime. By using this oxime as a key precursor and intramolecular nitrile oxide cycloaddition (INOC) as a key step, the total synthesis of (+)-Epilupinine was achieved successfully.In chapter 4, a series of chiral (2R,6R)-2-acetal-6-alkylpiperidines were synthesized by Pd/C catalyzed debenzylation of Betti base residue in the presence of 1,1,2-trichloroethane. By using them as precursors (alkyl = propyl, pentyl, hexyl), the total syntheses of indolizidine alkaloids, such as 167B, 195H and 209D, were finished within 3 steps and very high total yields.