Study On The Novel Synthesis Method Of The Nitrogen-containing Fused-heterocycle Compounds

Nitrogen-containing fused-heterocyclic compounds have good biological activities and play an important role in the treatment of human diseases.Therefore,it is of great significance to synthesize those compounds with novel structures and study their biological activities.In this thesis,we developed a novel synthetic method to construct tricyclic quinazolinone compounds with plane structure.At the same time,we also developed a novel multi-component dearomatization reaction to construct nitrogen-containing fused-heterocyclic derivatives.The following is the main content.1.Pd（II）-catalyzed carbonylative cyclization of N-aryl-2-aminopyrimidines with Mo（CO）₆ as a surrogate of carbon monoxideA convenient and efficient synthetic protocol is established for the preparation of pyrimidoquinazolinone through Pd（II）-catalyzed carbonylative cyclization of N-aryl-2-aminopyrimidines with Mo（CO）₆as carbon monoxide source.A series of 6H-pyrimido[2,1-b]quinazolin-6-one derivatives were obtained in good yields.The scale-up synthesis was investigated.2.Acid-promoted intermolecular cyclization reaction between guanosine and TMOPA simple and efficient synthetic method is established for the preparation of tricyclic nucleosides derivatives through the cyclization of purines with 1,1,3,3-tetramethoxypropane in the presence of Ac OH.A series of tricyclic acyclic nucleosides derivatives were obtained in moderate to excellent yields,including some antivirus drugs（acyclovir,ganciclovir,penciclovir,and valaciclovir）derivatives.This method has also been applied to the efficient synthesis of the endogenous fused ring nucleoside（M₁d G）and its derivatives.Additionally,the late-stage diversification of nucleotides has also been accomplished.3.A novel multi-component reaction involving nitrogen-containing fused-heterocyclic compounds,electrophiles NXS and alcohols.A novel multi-component reaction involving nitrogen-containing fused-heterocyclic compounds,electrophiles and nucleophiles to the synthesis of polysubstituted cyclic guanidine derivatives is reported.Two new C-O bonds,one new C-X bond and one new N-H bond were formed in one-pot reaction when NXS was used as the electrophile and alcohols as the nucleophiles.