Synthesis of Curcumin Analogs (2E,6E)-2-(4-Hydroxy-3-Methoxy-5-((Pyrrolidine)methyl)benzylidene) -6-(4-Methoxybenzylidene)Cyclohexane-1-one
Keywords:
curcumin, Manich base, pyrrolidine, synthesis, curcumin, Manich base, pyrrolidine, synthesis
Abstract
Curcumin is a potential compound to be developed. However, the clinical use of these compounds is limited due to their low stability and bioavailability. Therefore, to increase the pharmacological activity of curcumin, it is necessary to modify the chemical structure of curcumin. Curcumin analog compound (2E,6E)-2-(4-hydroxy-3-methoxy-5-((pyrrolidine)methyl)benzylidene)-6-(4-methoxybenzyliden)cyclohexane-1-on can be synthesized in 3 steps. Phase I, the reaction between p-methoxybenzaldehyde and cyclohexanone took place aldol condensation reaction with NaOH catalyst. Phase II, the Clasein-Schmidt reaction between compound 1 (the result of the synthesis of stage I) and vanillin involved dilute HCl as the catalyst. Phase III, reacting the results of the synthesis of phase II with Mannich pyrrolidine base by adapting the method used by Geschickter and Maeadow. Compound 3 as a result of purification was observed using Thin Layer Chromatography using Ethyl Acetate:Methanol (1:1) as an eluent to obtain Rf 0.46 and a melting range of 130-131 oC. The yield obtained was 51.52% with the characteristics of a reddish brown powder. This compound needs further identification using the Mass Spectrum and NMR.References
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Bala, S., Sharma, N., Kajal, A., Kamboj, S., & Saini, V. (2014). Mannich Bases: An Important Pharmacophore in Present Scenario. Intl J of Med Chem, 1-15.
Bandgar, B. P., Patil, S. A., Gacche, R. N., Korbad, B. L., Hote, B. S., Kinkar, S. N., & Jalde, S. S. (2010). Synthesis and biological evaluation of nitrogen-containing chalcones as possible anti-inflammatory and antioxidant agents. Bioorganic & medicinal chemistry letters, 20(2), 730-733.
Furniss, B. S., Hannaford, A. J., Rogers, V., Smith, P. W. G., & Tatchel, A. R. (1989). Vogel’s textbook of practical organic chemistry. 4th ed. London: Longman Group Ltd.
Geschickter, C. F., & Meadow, J. R. (1969). United States Patent No. 3.479.345.
Manohar, S., Khan, S. I., Kandi, S. K., Raj, K., Sun, G., Yang, X., Molina, A. D. C., Ni, N., Wang, B., & Rawat, D. S. (2013). Synthesis, antimalarial activity cytotoxic potential of new monocarbonyl analogues of curcumin. Bioorganic and Medicinal Chemistry Letters, 23(1), 112-116.
Prasetyaningrum, P.W. (2018). Sintesis analog kurkumin monokarbonil asimetrik tersubstitusi basa mannich dietilamin dan uji sitotoksisitas terhadap sel hela. Tesis, Univeristas Indonesia, Depok.
Prasetyaningrum, P.W., Bahtiar, A., Hayun, H. (2018). Synthesis and cytotoxicity evaluation of novel asymmetrical mono-carbonyl analogs of curcumin (AMACs) against Vero, HeLa, and MCF7 Cell Lines. Sci Pharm, 86(2), 25. http://doi.org/10.3390/scipharm8602002 5
Putri, T. N. (2018). Sintesis dan uji aktivitas antiinflamasi dan antioksidan in vitro analog kurkumin monokarbonil asimetrik tersubstitusi basa mannich morfolin. Tesis, Universitas Indonesia, Depok.
Putri, T. N., Bachtiar, A., Hayun, H. (2018). Synthesis, antioxidant, and antiinflammatory activity of morpholine Mannich base of AMACs ((2E,6E)-2-({4-hydroxy-3-[morpholin-4-yl)methyl] phenyl}methylidene)(phenylmethylidene)cyclohexan-1-one) and its analogs. J App Pharm Sci, 8,19-25. http://doi.org/10.7324/JAPS.2018.8503
Rahman, A. F. M. M., Ali, R., Jahng, Y., & Kadi, A. A. (2012). A Facile Solvent Free Claisen-Schmidt Reaction: Synthesis of α,α′-bis-(Substituted-benzylidene) cycloalkanones and α,α′-bis-(Substituted-alkylidene)cycloalkanones. Molecules, 17, 571-583.
Rahmawati, N., Hariyanti, H., Saputri, F.C., Hayun, H. (2020). Synthesis and Preliminary In Vitro Anti-inflammatory Evaluation of Mannich Bases Derivatives of 4’-Methoxy-substituted of Asymmetrical Cyclovalone Analogs. Indonesia J Pharm, 31(1), 35-41. http://dx.doi.org/10.14499/indonesianjpharm31iss1pp35
Roman, G. (2015). Mannich bases in medicinal chemistry and drug design. Eur J Med Chem, 89, 743-816.
Sujith, K.V., Rao, J.N., Shetty, P., & Kalluraya, B. (2009). Regioselective reaction: synthesis and pharmacological study of Mannich bases containing ibuprofen moiety. European journal of medicinal chemistry, 44(9), 3697-3702.
Thong-Ngam, D., Choochuai, S., Patumraj, S., Chayanupatkul, M., & Klaikeaw, N. (2012). Curcumin prevents indomethacin induced gastropathy in rats. World J Gastroenterol 18, 1479 84.
Zhang, Y., Zhao, L., Wu, J., Jiang, X., Dong, L., Xu, F., & Liang, G. (2014). Synthesis and evaluation of a series of novel asymmetrical curcumin analogs for the treatment of inflammation. Molecules, 19(6), 7287-7307.
Published
2023-07-31
How to Cite
Rahmawati, N., Fitriana, A., & Sholikha, M. (2023). Synthesis of Curcumin Analogs (2E,6E)-2-(4-Hydroxy-3-Methoxy-5-((Pyrrolidine)methyl)benzylidene) -6-(4-Methoxybenzylidene)Cyclohexane-1-one. Sainstech Farma: Jurnal Ilmu Kefarmasian, 16(2), 84-93. https://doi.org/https://doi.org/10.37277/sfj.v16i2.1578
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