Methodology On The Assembly Of Indoloazepine And Benzoazepine And Its Application In The Total Synthesis Of Arboflorine

Not only heterocyclic compounds are widespread in nature,but also natural and synthetic heterocyclic compounds have important and wide applications in the field of chemical and medical industry.In comparison with five-and six-membered nitrogen-containing heterocycles,the number of azepine compounds are relatively smaller.However,most alkaloids containing indoloazepine and benzoazepine skeleton possess potent biological activities,part of them have been developed as drugs for the treatment of various diseases.Therefore,to explore the methodology for the preparation of azepine compounds became one of the attractive projects in organic chemistry.Although some precedent methods own their advantages in the preparation of indoloazepine and benzazepine compounds with special substituents,limitation such as the difficulty to obtain the precursor still exists.In addition,even though several groups attempt to complete the total synthesis of alkaloid arboflorine which bearing indoloazepine moiety,no reports appeared until now.In this thesis,the following topics are included:(1)An efficient synthetic route was established to assemble indoloazepines by using a halocarbocyclization-triggered cascade reaction starting from enaminoesters/enaminones.Meanwhile,a new protocol was developed to prepare benzoazepine compounds in one-pot manner,which includes ?-halogenation of enaminoester,an intramolecular Friedel-Crafts cyclization and a ring expansion of halogenated tetrahydroisoquinoline.(2)A new route was designed for the total synthesis of alkaloid arboflorine,the key step of which is the newly-developed halocarbocyclization-triggered cascade reaction of enaminone,which provides an important indoloazepine intermediate.Further works are in progress.