Chiral Spirocyclic Phosphoric Acid-Catalyzed Asvmmetric Svnthesis Ofα-aminoalkylphosphonate Esters

As biologically active isosters of α-amino acids, optically active a-amino phosphonic acids and their phosphonate esters have attracted considerable attention in modern pharmaceutical chemistry because they have been found to act as antibiotics, antibacterial, and anti-HIV agents. In this thesis, the progress of the asymmetric synthesis of a-amino phosphonates was firstly reviewed. Then chiral spirocyclic phosphoric acid-catalyzed asymmetric phosphorylation reaction of imines and phosphites was developed to give a series of optically active a-amino-phosphonates. Finally we studied the molecular iodine-catalyzed multicomponent reaction to obtain some tetrahypydines derivatives. The research includes as followed:1. We reviewed the progress of the asymmetric synthesis of a-amino phosphonates through summarizing three synthetic methods, including stoichiometric asymmetric synthesis,transition metal/chiral ligands-catalyzed synthesis, and asymmetric organocatalysis.2. The racemic spirocyclic diphenol was resolved by inclusion of crystallization with N-benzylcinchonidinuim chloride to give the enantiopure spirocyclic diphenol. The latter acted as starting material to prepare chiral spirocyclic phosphoric acids through five synthetic steps.3. Through the research on chiral spirocyclic phosphoric acid-catalyzed asymmetric phosphorylation reaction of imines and phosphites, we found that the the best results could be obtained to give a-amino phosphonates in high yields (up to96%) and with excellent enatioselectivities (up to98%ee) when the imines derived from cinnamic aldehydes were used as the substrates under optimized conditions. The absolute configuration of products was determined. A plausible mechanism was proposed.4. Molecular iodine-catalyzed multicomponent reaction of β-ketoesters, amines and aromatic aldehydes to afford highly functionalized tetrahydropyridines has been studied.