Authors : Dr. Kokane Balaji Digambar

Volume/Issue : Volume 11 - 2026, Issue 7 - July

Google Scholar : https://tinyurl.com/mps98j4a

Scribd : https://tinyurl.com/mryt9mm7

DOI : https://doi.org/10.38124/ijisrt/26jul186

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were synthesized reacting acyclovir and the respective acid anhydride in dimethyl sulfoxide (DMSO), in solvents from renewable sources and without solvent (T 30°C). Yields in prodrugs after 10 min of reaction were 95% using DMSO as solvent. The purification methodology was very simple,. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain 95% yield in microwave oven. This oily biosolvent is not dermotoxic and the reaction crude can directly be used in topic formulations. Syntheses without solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and tetradecanoate yielding 98% conversion of reactants in 10 sec. In spite of requiring mild tempera ture (300 wat), substrate molar ratios were lowered to 1:1, thus conducing to a more efficient use of raw materials. The synthetic procedures were scaled up to a 500g batch (yield 98—99% isolated ester). These esters can be used as acyclovir prodrugs in topic formulations. The esters release from an oil/water micro-emulsion and a hydrogel formulation were tested with good results.

Keywords : Acyclovir Prodrug; Green Chemistry; Transdermal Formulation.

References :

1. De Clercq E., Field H. J., Br. J. Pharmacol., 147, 1—11 (2006).
2. Coen D. M., Schaffer P. A., Nat. Rev. Drug Discov., 2, 278—288 (2003).
3. Redoules D., Tarroux R., Périé J., Skin Pharmacol. Appl. Skin Physiol., 11, 183—192 (1998).
4. Anand B. S., Nashed Y. E., Mitra A. K., Curr. Eye Res., 26, 151—163 (2003).
5. Cross S. E., Roberts M. S., Curr. Drug Deliv., 1, 81—92 (2003).
6. Brown M. B., Martin G. P., Jones S. A., Akomeah F. K., Drug Deliv., 13, 175—187 (2006).
7. Vávrová K., Zbytovská J., Hrabálek A., Curr. Med. Chem., 12, 2273— 2291 (2005).
8. Finnin B. C., Morgan T. M., J. Pharm. Sci., 88, 955—958 (1999).
9. Kanikkannan N., Kandimalla K., Lamba S. S., Singh M., Curr. Med. Chem., 6, 593—608 (1999).
10. Spector T., Jones T. E., Beacham L. M. 3rd, Biochem. Pharmacol., 32, 2505—2509 (1983).
11. Krenitsky T. A., Hall W. W., de Miranda P., Beauchamp L. M., Schaef fer H. J., Whiteman P. D., Proc. Natl. Acad. Sci. U.S.A., 81, 3209— 3213 (1984).
12. Hardnen M. R., Wyatt P. G., Boyd M. R., Sutton D., J. Med. Chem., 33, 187—196 (1990).
13. Shao Z., Park G. B., Krishnamoorthy R., Mitra A. K., Pharm. Res., 11, 237—242 (1994).
14. Bando H., Takagi T., Yamashita F., Takakura Y., Hashida M., Pharm. Res., 13, 427—432 (1996).
15. Kim D. K., Lee N., Im G. J., Kim H. T., Kim K. H., Bioorg. Med. Chem., 6, 2525—2530 (1998).
16. Gao H., Mitra A. K., Magn. Reson. Chem., 37, 687—689 (1999).
17. Gao H., Mitra A. K., Synthesis-Stuttgart, (3), 329—351 (2000).
18. Stankova I., Schichkov S., Kostova K., Galabov A., Zeitsch. Natur. Section C-a J. Biosci., 65, 29—33 (2010).
19. Stankova I., Chuchkov K., Wutzler P., Schmidtke M., Nucleosides Nu cleotides Nucleic Acids, 29, 760—767 (2010).

20. Simeo Y., Sinisterra J. V., Alcantara A. R., Green Chem., 11, 855— 862 (2009).
21. Schrek R., Elrod L. M., Batra K. V., Ann. N. Y. Acad. Sci., 141, 202— 213 (1967).
22. Steinberg A., Ann. N. Y. Acad. Sci., 141, 532—550 (1967).
23. Blumenthal L. S., Fuchs M., Ann. N. Y. Acad. Sci., 141, 572—585 (1967).
24. De Regil R., Rodríguez-Bayón A., Sinisterra J. V., Process for the Manufacture of Acyclovir Prodrugs, Eur. Patent EP: 08 019 325.3, Oc tober, 2008.
25. Rodríguez-Bayón A. M., Trujillo-Casares S. H., Personal communica tion.
26. Rodríguez-Bayón A. M., Trujillo-Casares S. H., Proceedings of the 33rd Annual Meeting of Controlled Release Society, Versailles, 2009.
27. EPA, U.S. Environmental and Protection Agency, “Octanoamide, N,N Dimethyl and Decanamide, N,N-Dimethyl, Exemptions from the Requirement of a Tolerance,” 40 CFR Part 180, OPP-2005-0031, FRL 7698-3, DOCID, frl26fe05-14, 2005.