Synthesis and structural characterization of O-acyl and O-alkyl lawsone derivatives
DOI:
https://doi.org/10.65093/aci.v16.n2.2025.27Keywords:
1,4 naphthoquinones, lawsone, O-acyl derivatives, organic synthesisAbstract
Naphthoquinones are organic compounds with significant biological relevance and applications in medicinal and agricultural chemistry. This study reports the synthesis of known lawsone (1) derivatives 2‑acetoxy (2) and 2‑methoxy (3), together with four new O‑acyl derivatives (4-7) obtained through O‑alkylation and O‑acylation reactions. All compounds were fully characterized by FT‑IR, 1D and 2D NMR, and high‑resolution mass spectrometry (HRMS), confirming their structures unequivocally. Reaction yields ranged from 49.3% to 89.2%, with variations attributed to the nature of the acyl group. These findings provide a foundation for future biological assays aimed at evaluating antifungal activity against phytopathogens of agricultural importance.
Downloads
References
Bhupinder, P.S. & Khambay, P.J. (2000). The potential of natural naphthoquinones as the basis for a new class of pest control agents—An overview of research at IACR-Rothamsted. Crop Protection, 19, 597–601. https://doi.org/10.1016/S0261-2194(00)00078-8
Campos-Takaki, G.M., Steiman, R., Seigle-Murandi, F., Silva, A.A. & Bieber, L. (1992). Effect of medium composition on the antifungal susceptibility tests to lapachol, β-lapachone, phthiocol and its synthetic analogs. Rev. Microbiol., 23, 106–111.
Dash, A., Panda, J., Samanta, B. & Mohapatra, S. (2025). Advancements in synthetic methodologies and biological applications of lawsone derivatives. Organic & Biomolecular Chemistry, 23 (10), 2302-2322. https://doi.org/10.1039/D5OB00020C
De Simone, R.W., Currie, K.S., Mitchell, S.A., Darrow, J.W. & Pippin, D.A. (2004). Privileged Structures: Applications in Drug Discovery. Comb. Chem. High Throughput Screen., 7, 473–491. https://doi.org/10.2174/1386207043328544
Dekkers, J., Kooijman, H., Kroon, J. & Grech, E. (1996). 2-Hydroxy-1,4-naphthoquinone. Acta Cryst., C52, 2896–2899. https://doi.org/10.1107/S0108270196007664
Durán, A.G., Chinchilla, N., Molinillo, J.M. & Macías, F.A. (2018). Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and lawsone: A structure–activity relationship study in the search for natural herbicide models. Pest Manag. Sci., 74, 682–694. https://doi.org/10.1002/ps.4764
Dweck, A.C. (2002). Natural ingredients for colouring and styling. Int. J. Cosmet. Sci., 24, 287–302. https://doi.org/10.1046/j.1467-2494.2002.00148.x
Hui, Y., Khim Chng, E.L., Lin Chng, C.Y., Poh, H.L. & Webster, R.D. (2009). Hydrogen-Bonding Interactions between Water and the One- and Two-Electron-Reduced Forms of Vitamin K1: Applying Quinone Electrochemistry to Determine the Moisture Content of Non-Aqueous Solvents. J. Am. Chem. Soc., 131, 1523–1534. https://doi.org/10.1021/ja8080428
Lamoureux, G., Perez, A.L., Araya, M. & Agüero, C. (2008). Reactivity and Structure of derivatives 2-hydroxy-1,4-naphthoquinone (lawsone). J. Phys. Org. Chem., 21, 1022–1028. https://doi.org/10.1002/poc.1435
López, L., Leyva, E. & García de la Cruz, R.F. (2011). Las naftoquinonas: más que pigmentos naturales. Rev. Mex. Cienc. Farm., 42, 6–17.
Munday, R., Smith, B.L. & Munday, C.M. (2007). Structure–activity relationships in the haemolytic activity and nephrotoxicity of derivatives of 1,2- and 1,4-naphthoquinone. J. Appl. Toxicol., 27, 262–269. https://doi.org/10.1002/jat.1206
Ogawa, M., Koyanagi, J., Sugaya, A., Tsuda, T., Ohguchi, H., Nakayama, K., et al. (2006). Cytotoxic Activity toward KB Cells of 2-Substituted Naphtho[2,3-b]furan-4,9-diones and Their Related Compounds. Biosci. Biotechnol. Biochem., 70, 1009–1012. https://doi.org/10.1271/bbb.70.1009
Ravelo, A.G., Estevez-Braun, A., Chavez-Orellana, H., Perez-Sacau, E. & Mesa-Siverio, D. (2004). Recent Studies on Natural Products as Anticancer Agents. Curr. Top. Med. Chem., 4, 241–265. https://doi.org/10.2174/1568026043451500
Rostkowska, H., Nowak, M.J., Lapinski, L. & Adamowicz, L. (1988). 2-hydroxy-1,4-naphthoquinone; Experimental matrix isolation and theoretical Hartree-Fock and post Hartree-Fock study. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 54, 1091–1103. https://doi.org/10.1016/S1386-1425(98)00032-8
Rungrojrattikorn, K., Manuschai, J., Suwanhom, P., Kara, J., Lomlim, L. & Naorungroj, S. (2024). In vitro evaluation of 2-(chloroalkyloxy)naphthalene‑1,4‑dione derivatives as anticaries agents. ScienceAsia, 50 (5), Article 098. https://doi.org/10.2306/scienceasia1513-1874.2024.098
Shahid Khan, M. & Khan Zahid, H. (2005). Ab initio and semiempirical study of structure and electronic spectra of hydroxy substituted naphthoquinones. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 61, 777–790. https://doi.org/10.1016/j.saa.2004.04.027
Song, R., Yu, B., Friedrich, D., Li, J., Krautscheid, H.H., Huang, S.D. & Kim, M.-H. (2020). Naphthoquinone-derivative as a synthetic compound to overcome the antibiotic resistance of methicillin-resistant S. aureus. Commun. Biol., 3, 529. https://doi.org/10.1038/s42003-020-01261-0
Sujathan Nair, A., Sekar, M., Hua Gan, S., Kumarasamy, V., Subramaniyan, V., Seng Wu, Y., et al. (2024). Lawsone Unleashed: A Comprehensive Review on Chemistry, Biosynthesis, and Therapeutic Potentials. Drug Des. Dev. Ther., 18, 3295–3311. https://doi.org/10.2147/DDDT.S463545
Xiang, S., Li, Y., Khan, S. N., Zhang, W., Yuan, G. & Cui, J. (2025). Exploiting the anticancer, antimicrobial and antiviral potential of naphthoquinone derivatives: Recent advances and future prospects. Pharmaceuticals, 18 (3), 350. https://doi.org/10.3390/ph18030350
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
