DOI: https://doi.org/10.14710/jksa.27.8.354-362

Synthesis of Novel Ester-Based 5-Fluorouracil Derivatives

1Faculty of Pharmacy, University of Jember, Jember, East Java, Indonesia

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Jember, Jl. Kalimantan I/2 Jember 68121, East Java, Indonesia

Received: 6 Feb 2024; Revised: 2 Aug 2024; Accepted: 5 Aug 2024; Published: 31 Aug 2024.
Open Access Copyright 2024 Jurnal Kimia Sains dan Aplikasi under http://creativecommons.org/licenses/by-sa/4.0.

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Abstract
Fluorouracil (5-Fu, 1) is an antimetabolite cancer drug and the first-line drug of anticancer administration by WHO that has been widely used worldwide for more than 50 years. The development of 5-fluorouracil is an effort to obtain higher activity, decrease side effects, and create a specific target receptor compared to 5-fluorouracil. In this research, a series of novel 5-Fluorouracil (5-Fu) derivatives has been synthesized based on a benzoylation reaction (Schotten-Baumann reaction) of N1-hydroxylated 5-Fu called compound 2, 5-fluoro-1-(hydroxymethyl)-uracil. The benzoyl chloride substituents used in this research, including 3-chlorobenzoyl (4a), 2-chlorobenzoyl (4b), 3-nitrobenzoyl (4c), 4-methoxy benzoyl (4d), 4-trifluoromethylbenzoyl (4e), 3,4-dichlorobenzoyl (4f), and 4-nitrobenzoyl (4g) chloride become (4a-4f)-5Fu. This research meticulously examined the conditions (time and reaction temperature) at the second step of the synthesis reaction (esterification), ensuring the reliability of the results. The best synthesis conditions for 4a, 4b, 4c, 4d, and 4g compounds were found to be reflux at 40°C for 6 hours, whereas 4e and 4f compounds reactions were performed in an ice bath for 11 and 17 hours, respectively. All product syntheses, 4a-4g compound, were purified using column chromatography and eluted using eluent hexane: acetone (6:4), and the yields of 4a-4g compounds were around 61-79%. The pure compounds were characterized using FTIR and 1HNMR spectrometer, further validating the research. Based on these findings, it can be concluded that all 5-Fu derivatives can be synthesized using the Schotten-Baumann reaction method.
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Keywords: 5-Fluorouracil; Derivatives; Synthesis; Benzoylation
Funding: Hibah Bersaing Research Grant

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Section: Research Articles
Language : EN
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