Synthesis, Spectral Characterization, and Structural Modification of a Hesperetin-Derived N-Benzylacetamide
Keywords:
Synthesis, Hesperetin, Orange peel, UV-visible spectroscopy, FT-IR, ¹H NMRAbstract
Aim : This work aimed to synthesize and characterize a novel N-benzylacetamide derivative of hesperetin from Orange peel and evaluate its structural modification.
Materials Method: Intermediate 1 (75% yield) was produced by reacting hesperetin with ethyl bromoacetate in ethanol. Intermediate 2 (62% yield) was obtained after treatment with sodium carbonate in ethanol–water and acidification with hydrochloric acid. N-benzyl-2-[5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-oxochroman-7-yloxy]-acetamide, the last hesperetin derivative was synthesized by combining benzylamine with EDC/HOBt producing 48%. UV-visible spectroscopy, FT-IR, ¹H NMR, and mass spectrometry were used to confirm the structural and functional characteristics of the synthesized chemical.
Results: The synthesized compound was characterized using UV–visible spectroscopy, FT-IR, ¹H NMR, and mass spectrometry to confirm its structural and functional properties. The synthesis yielded the target hesperetin derivative with an overall efficiency (final yield 48%). UV–visible analysis showed a λmax at 288 nm. FT-IR spectra confirmed the presence of key functional groups, including O–H, C=O, and C–O. ¹H NMR spectra confirmed that the benzylacetamide molecule was successfully incorporated. Mass spectrometry exhibited a molecular ion peak at m/z 475.9 ([M+Na]⁺), confirming the expected molecular structure.
Conclusion: A new N-benzylacetamide derivative of hesperetin was effectively synthesized and described in this study. Without changing the core flavanone, spectroscopic tests verified the structural alteration
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References
[1] Uehara, M. (2006). Prevention of osteoporosis by foods and dietary supplements. Hesperidin and bone metabolism. Clinical Calcium, 16(10), 1669-1676.
[2] Gómez-Mejía, E., Rosales-Conrado, N., León-González, M. E., & Madrid, Y. (2019). Citrus peels waste as a source of value-added compounds: Extraction and quantification of bioactive polyphenols. Food chemistry, 295, 289-299.
[3] Jokić, S., Molnar, M., Cikoš, A. M., Jakovljević, M., Šafranko, S., & Jerković, I. (2020). Separation of selected bioactive compounds from orange peel using the sequence of supercritical CO2 extraction and ultrasound solvent extraction: Optimization of limonene and hesperidin content. Separation science and technology, 55(15), 2799-2811.
[4] Obafaye, R. O., & Omoba, O. S. (2018). Orange peel flour: A potential source of antioxidant and dietary fiber in pearl‐millet biscuit. Journal of food biochemistry, 42(4), e12523.
[5] Anticona, M., Blesa, J., Frigola, A., & Esteve, M. J. (2020). High biological value compounds extraction from citrus waste with non-conventional methods. Foods, 9(6), 811.
[6] Meléndez-Martínez, A. J., Mandić, A. I., Bantis, F., Böhm, V., Borge, G. I. A., Brnčić, M., ... & O’Brien, N. (2022). A comprehensive review on carotenoids in foods and feeds: Status quo, applications, patents, and research needs. Critical Reviews in Food Science and Nutrition, 62(8), 1999-2049.
[7] Panić, M., Stojković, M. R., Kraljić, K., Škevin, D., Redovniković, I. R., Srček, V. G., & Radošević, K. (2019). Ready-to-use green polyphenolic extracts from food by-products. Food chemistry, 283, 628-636.
[8] Kim, D. S., & Lim, S. B. (2020). Semi-continuous subcritical water extraction of flavonoids from Citrus unshiu peel: Their antioxidant and enzyme inhibitory activities. Antioxidants, 9(5), 360.
[9] Crespo, M. E., Galvez, J., Cruz, T., Ocete, M. A., & Zarzuelo, A. (1999). Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS. Planta medica, 65(07), 651-653.
[10] Wilmsen, P. K., Spada, D. S., & Salvador, M. (2005). Antioxidant activity of the flavonoid hesperidin in chemical and biological systems. Journal of agricultural and food chemistry, 53(12), 4757-4761.
[11] Tempesti, T. C., Alvarez, M. G., de Araújo, M. F., Catunda Júnior, F. E. A., de Carvalho, M. G., & Durantini, E. N. (2012). Antifungal activity of a novel quercetin derivative bearing a trifluoromethyl group on Candida albicans. Medicinal Chemistry Research, 21(9), 2217-2222.
[12] Elshazly, S. M., & Mahmoud, A. A. (2014). Antifibrotic activity of hesperidin against dimethylnitrosamine-induced liver fibrosis in rats. Naunyn-Schmiedeberg's archives of pharmacology, 387(6), 559-567.
[13] Kapoor, M. P., Moriwaki, M., Minoura, K., Timm, D., Abe, A., & Kito, K. (2022). Structural investigation of hesperetin-7-O-glucoside inclusion complex with β-cyclodextrin: a spectroscopic assessment. Molecules, 27(17), 5395.
[14] Mistry, B., Patel, R. V., & Keum, Y. S. (2017). Access to the substituted benzyl-1, 2, 3-triazolyl hesperetin derivatives expressing antioxidant and anticancer effects. Arabian Journal of Chemistry, 10(2), 157-166.
[15] Minakshi Verma and Alok Kumar Dash*(2025) Recent Advances in Nanoformulations of Citrus Bioactives & Potential Health Benefits, Micro and Nanosystems, Bentham Science Publishers ,ISSN:1876-4037,Published 07 January, 202 Vol. 17, No. 3, 2025,(
[16] Sant, A., Modanwal, S., Parveen, S., Ahtsham, A., Porwal, K., Mishra, N., ... & Bhatia, S. (2025). Value Addition to Citrus maxima Peels: Extraction and Modification of Naringenin into Hydrazones Derivatives for Anti‐Breast Cancer and Osteogenic Activity via In Vitro and In Silico Studies. Chemistry & Biodiversity, 22(12), e01059.
[17] Nectoux, A. M., Abe, C., Huang, S. W., Ohno, N., Tabata, J., Miyata, Y., ... & Matsui, T. (2019). Absorption and metabolic behavior of hesperidin (rutinosylated hesperetin) after single oral administration to Sprague-Dawley rats. Journal of Agricultural and Food Chemistry, 67(35), 9812-9819.
[18] Yamamoto, M., Jokura, H., Hashizume, K., Ominami, H., Shibuya, Y., Suzuki, A., ... & Shimotoyodome, A. (2013). Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities. Food & function, 4(9), 1346-1351.
[19] Luo, W., Wang, T., Hong, C., Yang, Y. C., Chen, Y., Cen, J., ... & Wang, C. J. (2016). Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents. European journal of medicinal chemistry, 122, 17-26.
[20] Wang, B., Mai, Y. C., Li, Y., Hou, J. Q., Huang, S. L., Ou, T. M., ... & Huang, Z. S. (2010). Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors. European journal of medicinal chemistry, 45(4), 1415-1423.
[21] Ellman, G. L., Courtney, K. D., Andres Jr, V., & Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7(2), 88-95.
[22] Li, B., Huang, A. L., Zhang, Y. L., Li, Z., Ding, H. W., Huang, C., ... & Li, J. (2017). Design, synthesis and evaluation of hesperetin derivatives as potential multifunctional anti-Alzheimer agents. Molecules, 22(7), 1067
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