Studies On The Asymmetric Synthesis Of δ-amino Acid Derivatives And Their Application In The Synthesis Of Spirocyclic Oxindoles

Amino acids,the building blocks of proteins and peptides in biological systems,have played important roles.The chiral δ-amino acid derivatives,such asδ-amino-β-carbonyl compounds,are not only the common molecular fragments in active natural products but also important intermediates in organic synthesis for piperidines,prolines and quinolizidines.Vinylogous Mannich reaction(VMR)is one of the most efficient method to generate δ-amino-β-carbonyl compounds.This dissertation includes four chapters.In the first chapter,the preparation and applications of chiral sulfinimines,especially chiral N-tert-butylsulfinimine,were summarized with the focus on applications of sulfinimines in the synthesis of amino acids.In the second chapter,a diastereoselective vinylogous Mannich reaction between the N-tert-butanesulfinyl imines and dioxinone-derived lithium dienolate was developed.35 examples were provided with excellent yields and high diastereoselectivities.The starting materials of the method were cheap and easily obtained.Spirocyclic oxindoles are the structural motifs frequently found in natural products and biologically active molecules.In the third chapter,a method for the synthesis of spirocyclic(pyrrole)oxindoles from isatinimines was developed.The key step was the nucleophilic addition of phenyl lithium to isatinimines followed by intramolecular reductive amination.13 spirocyclic(pyrdine)oxindoles were prepared successfully based on δ-amino acid derivatives synthesised in chapter two.16 compounds of spirocyclic oxindole-imidazole derivatives were also synthesized.The last chapter was the study on the synthesis of Mitomycin alkaloids.An important aziridine intermediate was successfully synthesized via the nucleophilic addition of chloromethyl anion towards N-tert-butanesulfinyl imines.