Studies On Synthesis Of 3,9-Diazaasteranes In Confined Media

The 3,9-diazatetraasterane has attracted the attention of researchers for its anti-HIV protease activity and anti-tumor and other physiological pharmacological activities.This thesis focuses on the synthesis of 3,9-diazatetraasteranes in confined media.In order to establish an efficient synthetic method of 3,9-diazatetraasterane,the studies on[2+2]photocycloaddition of 1,4-dihydropyridines in confined media were conducted systematically.The results of synthesis of 3,9-diazatetraasteranes in confined media will provide theoretical and experimental basis for their pharmacological applications in anti-viral and anti-tumor activity.It will provide theoretical reference for synthesis of tetraasteranes and polyhedrons.The studies on the synthesis of 1,4-dihydropyridine derivatives were the 4-aryl-1,4-dihydropyridines（1）and 1,4-dihydropyridines（2）as tatget compounds,the ethyl propionate as synthon,the condensation of aldehydes and amines as reaction mechanism.The microwave synthesis was used to improve the synthesis of ethyl 1,4-dihydropyridines-3,5-dicarboxylate in higher efficient and convenient way.The results show that the yields of the 1,4-dihydropyridines were increased from 40%to 70%,the reaction time significantly shortened to 30 min.The studies on the synthesis of 3,9-diazatetraasteranes in confined media were based on the 4-phenyl-1,4-dihydropyridine as the model compound.The main factors influencing the[2+2]photocycloaddition in confined media,including the types of confined media,light source and wavelength,solvent type,solution concentration,the ratio of substrate to confined media,illumination time and other factors,were investigated.The results show that the synthetic method of 3,9-diazatetraasteranes inγ-cyclodextrin was an efficient one.A series of 3,9-diazatetraasteranes（3）were synthesized from 4-aryl-1,4-dihydropyridine by a[2+2]photocycloaddition with higher selectivities and the yields of about 80%.The studies on the synthesis of 3,9-diazatetraasteranes（4）inγ-cyclodextrin were that 4-unsubstituted-1,4-dihydropyridines（2）as raw material,the 3,9-diazatetraasteranes（4）as target compounds were synthesized by the established method inγ-cyclodextrin.The results indicated that the confined media can promote the[2+2]photocycloaddition of 1,4-dihydropyridine（2）,the yields were improved from about60%to about 80%.The substituent effects of 1,4-dihydropyridines（2）has an important influence on the[2+2]photocycloaddition.The N-aryl-1,4-dihydropyridine（2）can form the 3,9-diazatetraasteranes（4）and N-benzyl-1,4-dihydropyridine（2）cannot form4 but the syn-dimeric intermediates.Through the studies on the synthesis of 3,9-diazatetraasteranes in confined media,an efficient synthetic method of 3,9-diazatetraasterane inγ-cyclodextrin was established,15 new compounds were obtained including 6 new 1,4-dihydropyridines and 9 novel3,9-diazatetraasteranes and syn-dimeric intermediates.All new compounds were characterized by ¹H and ¹³C NMR spectroscopy,HRMS and X-ray diffraction.