A Synthesis of Novel Tetracyclic Azocino[4,3‐b]Indole Framework: Combined Spectroscopic, DFT, Molecular Docking, and ADMET Analysis

ABSTRACT The paper describes a new synthetic method for the 1,5‐methanoazocino [4,3‐b]indole. Starting from 2,3,4,9‐tetrahydrospiro[1H‐carbazole‐1,2’‐[1,3]dithiolan]‐4(9H)‐one I with (1,3‐dithiolan‐2‐yl)methanamine, reduction of imine II with NaBH 4 yielded to the amine and benzoylation, N‐((1,3‐dithiolan‐2‐yl)methyl)‐N‐(2,3,4,9‐tetrahydrospiro[carbazole‐1,2'‐[1,3]dithiolan]‐4‐yl)benzamide III . Compounds IV and V were completed through several steps from III . The resulting structure V underwent an intramolecular aldol reaction using NaH as a base for the cyclization of 2‐benzoyle‐4‐hydroxy‐1,2,3,4,5,7‐hexehydro‐1,5‐methanoazocino[4,3‐ b ]indole‐6‐one VI , which represents the tetracyclic skeleton of Strychnos alkaloids. Besides, quantum chemical computations were conducted on compounds I–VI . Regarding structural parameters and spectroscopic characterization, the experimental and computational data were found to be in good agreement. Also, ADMET, bioavailability, and drug‐likeness properties of the data set were determined to provide comprehensive information on structure‐activity relationships. The interactions of I–VI against DNA gyrase of E. coli , CYP51 from Candida glabrata , and leukemia inhibitory factor were evaluated with molecular docking for foresight into the possible bioactivities. This comprehensive work hopefully to provide the structural, physical, and chemical properties, which would be important to optimizing the related properties of the molecular systems for biomedical purposes.