Study On Synthesis And Bioactivity Of Tetrahydro-?-carbolines

Tetrahydro-?-carbolines(THBCs)alkaloids,which with a nitrogen atom on the side ring at the beta position of the nitrogen in indole,are a large group of nature and synthetic indole alkaloids.Tetrahydro-?-carbolines alkaloids mainly exist in the root,peels,leaves,seeds of plants such as Zygophyllaceae,Smaroubaceae,et al,and marine organisms.Tetrahydro-?-carbolines as well as relavent scaffolds(e.g.?-carbolines)are privileged structural motifs present in many natural products and medicinally valuable molecules.Their broad spectrum of biological and pharmacological profiles such as antitumor,antiviral,antimicrobial and antiparasitic activities.The most commonly used methods to access tetrahydro-?-carbolines rely on Pictet-Spengler condensations of tryptamine or tryptophan with aldehydes or ketones.Of note,such methods are oftenly applied to the synthesis of C1-or C3-functionalized THBCs.Comparably,obtaining 4-functionalized THBCs remains a challenging task,and multistep procedures are normally required.Recently,Rh(?)-azavinylcarbene,which is readily generated from N-sulfonyl-1,2,3-triazole through denitrogenative reaction,has evolved into a capable intermediate for the synthesis of various nitrogen heterocycles.In light of the importance of THBCs and relevant scaffolds in organic and medicinal chemistry,as well as the fact that only limited methods exist for their synthesis,we sought to develop a new entry to the aforementioned heterocycles based on the emerging Rh-AVC chemistry.In this paper,we started our work around the chemical synthesis of tetrahydro-?-carbolines,and our work focus on the synthetic methodology of tetrahydro-?-carbolines,the structural diversity derivatization,biological activity,and the study of structure-activity relationship of tetrahydro-?-carbolines.In the synthesis methodology,we have developed an efficient method for theconstruction of 4-substituted tetrahydro-?-carbolines through a novel Rh(?)-catalyzed intramolecular annulation of 1-sulfonyl-1,2,3-triazoles with indoles.An operationally simple one-pot three-steps protocol was also established,which enable the rapid access of the title compounds from readily available starting materials.The potential utility of the present chemistry was demonstrated by a short formal synthesis of Oxopropaline G.All of the target compounds were by1H-NMR,13C-NMR and HRMS.The in vitro inhibitory activity of the target compounds were evaluated against the Hela cell lines,which have good prospect for further development.Most of the test compounds showed growth inhibitory activity against the Hela cell lines.What is more,the target compounds,especially 11 e,11f,11 l,11m,11 p,11r and 11 v,exhibited good anti-Hela cell activity in the laboratory,their anti-Hela cell activities were as follows65.6%,73.7%,69.5%,53.9%,61.9%,55.7% and 53.7% in vitro,at 40 ?g/mL.The preliminary structure-activity relationships of these types of compounds have been investigated.