One-Step Synthesis of 3-(diarylmethyl) indole Derivatives as -glucosidase Inhibitors
Abstract
In this research, a one-step synthesis of 3-(diarylmethyl)indoles (4) via Bi(OTf)3-catalyzed one-pot three-component coupling reaction of indoles, aldehydes and tertiary aromatic amines was developed. After an extensive study, we found that the reaction employing 10 mol% of Bi(OTf)3 under refluxing dichloroethane gave the corresponding 3-(diarylmethyl)indoles (4) in moderate to high yields. The effect of substituents at C-4 position of benzaldehyde derivatives was also studied. The results showed that benzaldehyde derivatives with electron-withdrawing substituents at C-4 position of benzene ring such as Cl, Br and nitro gave the desired products in higher chemical yields than those of electron-donating substituents such as OMe and OH. Furthermore, the synthesized compounds were also evaluated for their a-glucosidase inhibition and the compound 4g exhibited promising a-glucosidase inhibitory activity (65.47 ± 0.22% of inhibition at 1.0 mM). Keywords : 3-(Diarylmethyl)indoles, Bi(OTf)3, a-Glucosidase inhibitory activityReferences
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Ollevier, T. (2012). In Bismuth-mediated organic reaction; Springer-Verlag: Heidelberg.
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Sibmooh, N. (2010). Pharmacology: Principles and Exercises. (2) Bangkok: Mahdol University. (in Thai)
Suzuki, H., & Matano, Y. (2002). In Organobismuth Chemistry; Elsevier: Amsterdam.
Zhang, X., Zhang, X., Li, N., Xu, X., Qiu, R., & Yin, S. (2014). Synthesis and structure of an air-stable binuclear
complex of bis(ethylcyclopentadienyl)zirconium perfluorooctanesulfonate and its catalytic application in
one-pot three-component aza-Friedel–Crafts reactions. Tetrahedron Letters, 55, 120–123.
/-glycosidase inhibitory effects. Bioorganic & Medicinal Chemistry Letters. 22, 7499-7503.
Eichler, J., Lucka, A.W., Pinilla, C., & Houghten, R.A. (1995). Novel -glucosidase inhibitors identified using
multiple cyclic peptide combinatorial libraries. Molecular Diversity, 1, 233-240.
Liu, J., He, T., & Wang, L. (2011). FeCl3 as Lewis acid catalyzed one-pot three-component aza-Friedel-Crafts
reactions of indoles, aldehydes, and tertiary aromatic amines. Tetrahedron, 67, 3420-3426.
Khan, M., Yousaf, M., & Wadood, A. (2014). Discovery of novel oxindole derivatives as potent -glucosidase
inhibitors. Bioorganic & Medicinal Chemistry, 22, 3441-3448.
Kothandapani, J., Ganesan, A., Vairaprakash, P., & Ganesan, S.S. (2015). Copper(II) chloride assisted aryl
exchange in arylmethanes: a simple and efficient route to triarylmethane derivatives. Tetrahedron Letters.
56, 2238–2242.
Kumar, A., Sharma, S., & Maurya, R.A. (2009). A novel multi-component reaction of indole, formaldehyde, and
tertiary aromatic amines. Tetrahedron Letters, 50, 5937-5940.
Najafi., E& Behbahani, F.K. (2017). Three-component synthesis of 3-(diarylmethyl)indoles using Fe(ClO4)3/SiO2 as
catalyst. Russian Journal of Organic Chemistry, 53, 454–458.
Ollevier, T. (2012). In Bismuth-mediated organic reaction; Springer-Verlag: Heidelberg.
Ollevier T. (2013). New trends in bismuth-catalyzed synthetic transformations, Organic & Biomolecular Chemistry.
11, 2740-2755.
Sibmooh, N. (2010). Pharmacology: Principles and Exercises. (2) Bangkok: Mahdol University. (in Thai)
Suzuki, H., & Matano, Y. (2002). In Organobismuth Chemistry; Elsevier: Amsterdam.
Zhang, X., Zhang, X., Li, N., Xu, X., Qiu, R., & Yin, S. (2014). Synthesis and structure of an air-stable binuclear
complex of bis(ethylcyclopentadienyl)zirconium perfluorooctanesulfonate and its catalytic application in
one-pot three-component aza-Friedel–Crafts reactions. Tetrahedron Letters, 55, 120–123.
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2019-09-17
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