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. 2023 Dec 30;78(6):1753-1761.
doi: 10.32592/ARI.2023.78.6.1753. eCollection 2023 Dec.

Synthesis of Remdesivir Derivate as a Generation of Anti-COVID-19 Drugs Through Acetylation Reactions

R Sumardi  1 , Y Rifai  1 , G Alam  1
Affiliations

Synthesis of Remdesivir Derivate as a Generation of Anti-COVID-19 Drugs Through Acetylation Reactions

R Sumardi et al. Arch Razi Inst. .

Abstract

Remdesivir, a competitive inhibitor of viral RNA-dependent RNA polymerase, is the drug of choice for anti-COVID-19 treatment. However, the instability of these substances in plasma raises doubts about their therapeutic potency. Additionally, SARS-CoV-2-infected cells may exhibit a variety of antiviral behaviors due to intricate activation pathways. Therefore, this study aimed to develop a synthesis for the remdesivir derivative. The remdesivir derivative was synthesized using acetyl chloride as a reagent in a ratio of 1:3 in dichloromethane and tetrahydrofuran solvent at 30°C for 6 h. Thin-layer chromatography and spectrophotometers (1H NMR and 13C NMR) were used to identify the produced molecule, which was a brownish-yellow crystalline powder. The results of the synthesis yielded 0.8 gr (77.34%), and the Rf value of the remdesivir derivate was 0.54. The characterization with 1H NMR at δ2.5 ppm (3H, s) indicated the presence of a proton in the H-C-C=O structure caused by the substitution of the acetyl group in the remdesivir structure. The 13C NMR data indicated the presence of aromatic carbons, alkenes, C≡N, and carbon bonds with electronegative O. This remdesivir derivate chemical can be a potential candidate for an anti-COVID-19 drug that has more potency because it has substitutions of acetyl groups at positions 2' and 3' in the structure of remdesivir.

Keywords: Acetyl chloride; Acetylation; COVID-19; Remdesivir; Remdesivir derivate; Synthesis.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Synthesis of  2-ethylbutyl (2S)-2- [[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-diacetyloxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
Figure 2
Figure 2
The mechanism of the acetylation reaction of the compound 2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-diacetyloxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
Figure 3
Figure 3
TLC results for remdesivir compounds (left) and remdesivir derivatives (right)
Figure 4
Figure 4
1H NMR results for remdesivir derivatives
Figure 5
Figure 5
13C NMR results for remdesivir derivatives
See this image and copyright information in PMC

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