Bis-indolylation of aldehydes and ketones using silica-supported FeCl₃: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites

Abstract

Silica supported FeCl3 catalyzed simple protocol for the synthesis of bis-indolylmethanes was explored via grindstone chemistry. Synthesized compounds were screened virtually as inhibitor by targeting the binding site of SARS-CoV-2 main protease enzyme.

Synthesis of Bis(3‐indolyl)methanes Mediated by Potassium tert‐Butoxide

“… [14] Other examples also include the use of metal‐free oxidative reactions. [ 15 , 16 ] Recently, several examples have been reported using aryl amines ( 1 ), [17] aldehydes ( 2 ),[ 18 , 19 , 20 , 21 , 22 ] ketones ( 3 ),[ 23 , 24 ] benzyl amines ( 4 )[ 16 , 25 ] and benzyl alcohols ( 5 )[ 26 , 27 , 28 ] as starting materials (Scheme 1 ).…”

Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach

“… 7 , 11 , 33 , 34 Interestingly, most methods utilize 3-indole aromatic alcohols to afford symmetrical and unsymmetrical 3,3′-BIMs using a condensation strategy with appropriate nucleophiles. 19 , 35 In addition, the most common reaction protocols used in the synthesis include expensive and excess amounts of catalysts such as Cu-catalysts, 36 TsOH, Ga(OTf) 3 , Zn(OTf) 2 , etc. 37 − 39 Several catalytic pathways were also developed to afford BIMs, which includes Bronsted or Lewis acid, methanol, iodine, electrolysis methods, metal salts, visible light, and enzymes.…”

“… − A unique structure of this bioactive intermediate contains two indole units which are responsible for exhibiting a range of essential biological activities such as anti-neurodegenerative, anti-inflammatory, anticancer, antibiotic, insecticidal, antimicrobial, antifungal, and antioxidant properties (Figure ). ,− Interestingly, some of these BIM derivatives are used as a sedatives in the treatment of AIDS, chronic fatigue, irritable bowel syndrome, and cancer, while bis­(indolyl)­arylmethane-bearing compounds are used as drugs for Parkinson’s disease, obesity, and bacterial and oncolytic viruses. ,− In addition, BIMs have also been found to have the potential to normalize abnormal cell growth associated with cervical dysplasia …”

“…As a result of this surge, numerous methods have been devised for the production of naturally occurring BIMs and their functionalized analogues (see Scheme ). ,,, Interestingly, most methods utilize 3-indole aromatic alcohols to afford symmetrical and unsymmetrical 3,3′-BIMs using a condensation strategy with appropriate nucleophiles. , In addition, the most common reaction protocols used in the synthesis include expensive and excess amounts of catalysts such as Cu-catalysts, TsOH, Ga­(OTf) 3 , Zn­(OTf) 2 , etc. − Several catalytic pathways were also developed to afford BIMs, which includes Bronsted or Lewis acid, methanol, iodine, electrolysis methods, metal salts, visible light, and enzymes. − Moreover, solid acidic catalysts such as Amberlyst, montmorillonite clay K-10, TiO 2 , ZrOCl 2 /SiO 2 , HClO 4 –SiO 2 , and P 2 O 5 /SiO 2 have also been investigated so far. − Over the last decades, methods for fabricating symmetrical and unsymmetrical 2,3′- and 3,3′-BIMs have primarily focused on the indolylation of 3-indolylmethyl alcohol, sulfone, malononitrile, 2,4,6-trimethoxybenzene, etc. with indole derivatives. − Although the divulged methodologies are phenomenal, they have some downsides, such as the need for expensive and higher catalytic loading, harsh reaction conditions, time-consuming reaction procedures, use of hazardous organic solvents, inadequate yields, and a constrained substrate scope.…”

The Synthesis of 2,2-BIS(1-INDOL-3-YL)Acenaphthylene-1(2)-Ones Using Nanocatalysis: Fluorescent Sensing for Cu2+ Ions

“…The bis-indoles structure has been interested in organic and medicinal chemistry, which have used for the synthesis of various pharmacological materials such as anti-malaria, inhibitors of HIV-1, anti-microbial, anti-inflammatory, anti-bacterial, anti-cancer, and COVID-19 inhibitor (Fig. 1) [70][71][72][73][74][75][76]. As well as the bis-indole derivatives have optical properties, which can detect via numerous methods in various environments containing inorganic ions and heavy metals (Fig.…”