Cinnamic Esters of Acyclovir-Synthesis and Biological Activity

Stankova, Ivanka; Chuchkov, Kiril; Wutzler, Peter; Schmidtke, Michaela

doi:10.1080/15257770.2010.518185

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…To the best of our knowledge, the syntheses of long chain esters of acyclovir (laurate and palmitate) have been referenced only in the Gao et al 17) review in which yields of 37% are reported. Recently, Stankova et al 18,19) described the synthesis of acyclovir esters with peptidomimetics or with cinnamic acid using coupling reagents and evaluated in vitro for their antiviral activity against the replication of Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2).…”

Section: Regular Articlementioning

confidence: 99%

New Green Synthesis and Formulations of Acyclovir Prodrugs

Regil‐Hernandez

Martinez‐Lagos

Rodríguez-Bayón

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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Different 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°03؍‬C). Yields in prodrugs after 10 min of reaction were Ͼ Ͼ95% using DMSO as solvent. The purification methodology was very simple, shorter and greener than previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain Ͼ Ͼ95% yield at 24 h. 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 Ͼ Ͼ98% conversion of reactants in 30 min. In spite of requiring mild temperature (65°C), 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 300 g 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.

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Section: Regular Articlementioning

confidence: 99%