DDQ/Fe(NO₃)₃-Catalyzed Aerobic Synthesis of 3-Acyl Indoles and an In Silico Study for the Binding Affinity of N-Tosyl-3-acyl Indoles toward RdRp against SARS-CoV-2

Abstract

In the present study, we herein report a DDQ-catalyzed new protocol for the synthesis of substituted 3-acylindoles. Being a potential system for virtual hydrogen storage, introduction of catalytic DDQ in combination with Fe(NO3)3·9H2O and molecular oxygen as co-catalysts offers a regioselective oxo-functionalization of C-3 alkyl-/aryllidine indolines even with scale-up investigations. Intermediate isolation, their spectroscopic characterization, and the density functional theory calculations indicate that the method involves dehydrogenative allylic hydroxylation and 1,3-functional group isomerization/aromatization followed by terminal oxidation to afford 3-acylindoles quantitatively with very high regioselectivity. This method is very general for a large number of substrates with varieties of functional groups tolerance emerging high-yield outcome. Moreover, molecular docking studies were performed for some selected ligands with an RNA-dependent RNA polymerase complex (RdRp complex) of SARS-CoV-2 to illustrate the binding potential of those ligands. The docking results revealed that few of the ligands possess the potential to inhibit the RdRp of SARS-Cov-2 with binding energies (−6.7 to −8.19 kcal/mol), which are comparably higher with respect to the reported binding energies of the conventional re-purposed drugs such as Remdesivir, Ribavirin, and so forth (−4 to −7 kcal/mol).

Oxy‐ and Chloroarylation Pathways in Gold‐Mediated Cyclization of 2‐Aminoaryl‐3‐arylpropargyl‐benzenesulfonamides

“…The authors have cited additional references within the Supporting Information (Ref. [23][24][25][26][27][28][29][30]).…”

Design and Synthesis of Indazole–Indole Hybrid via tert-Butyl Nitrite Mediated Cascade Diazotization/Isomerization/Cyclization

“…It was reported that N -sulfonamide indole derivatives possess interesting pharmaceutical activities such as antibacterial and antioxidant, properties, and hence N -tosyl indole–indazole will have significant pharmaceutical properties. However, since naturally occurring indoles lack protecting groups, we also carried out the detosylation of 5a using a solution of 50 mol % sodium hydroxide (NaOH) in methanol–water (1:1) under reflux conditions to obtain the detosylated product 5a′ in 90% yield (Scheme , 5a′ ).…”