Studies On The Synthesis Of Tetrahydroisoquinoline And Tetrahydro-?-carboline

Tetrahydroisoquinoline and tetrahydro-?-carboline are not only privileged structures found in many natural bioactive products,but also important synthons for the construction of natural-like products,which provide structurally varied compounds for pharmaceutical screening.The development of new methods for the synthesis and modification of these two structures have attracted extensive attentions in recent years.Despite the great achievements have been made,there are still a lack of simple and efficient methods for the one step synthesis of some special tetrahydroisoquinoline and tetrahydro-?-carboline.Consequently,the development of a simple,mild,and direct method for the synthesis of these structures is the current focus in medicinal organic chemistry.In this thesis,we have developed several new strategies,which could efficiently construct three different types of tetrahydroisoquinoline and tetrahydro-?-carboline.In the first part,we summarized the biological activities of tetrahydroisoquinoline and tetrahydro-?-carboline compounds and their synthesis methods.In the second part,we mainly introduced several synthesis strategies in detail:Firstly,the synthesis of C1-indole-isoquinoline compounds were accomplished by asymmetric dearomatizing reaction of isoquinoline catalyzed by chiral phosphoric acid.In the following work,we constructed a series of C1-isobenzofuranone-tetrahydroisoquinoline derivatives by using the photocatalytic radical-radical coupling reaction between N-aryl tetrahydroisoquinoline and o-benzaldehyde.Further biological evaluation showed that some of these compounds had lower IC₅₀ value and showed a better anti-tumor activity.Finally,asymmetric carboline-imidazolidin-5-ones compounds were synthesized by means of an ring opening rearrangement of the?-amino-?-lactams intermediates formed by carbacoline and azlactones under the catalysis of chiral phosphoric acid.The third part is the summary of our work and the further prospect of related research.