Synthesis of acyclovir, ganciclovir and their prodrugs: A review

Abstract

This review article deals with the synthetic methods of acyclovir, ganciclovir and their prodrugs. Based on the starting materials, three main routes to acyclovir and ganciclovir are described, including N9- regioselective synthesis. Prodrug approaches to increase the bioavailability included esterification, phosphorylation of acyclic fragment and oxidation of 6-deoxy acyclovir by xanthine oxidase. 1. Introduction. 2. Synthesis of Acyclovir and Ganciclovir. 2.1. Synthesis from Purines. 2.1.1. From O-6- Oxopurines. 2.1.1.1. Synthesis of Acyclovir. 2.1.1.2. Synthesis of Ganciclovir. 2.1.2. From O-6-Substituted Purines. 2.1.3. From C-6- Chloropurines. 2.1.4. From C-6-Sulfurpurines. 2.2. Synthesis from Furazanopyrimidines. 2.3. Synthesis from Imidazoles. 3. Synthesis of Prodrugs of Acyclovir and Ganciclovir. 3.1. Simple Aliphatic Ester Prodrugs. 3.1.1. Acyclovir Prodrugs. 3.1.2. Ganciclovir Prodrugs. 3.2. Water-Soluble Ester Prodrugs. 3.3. Phosphate Prodrugs. 3.4. 6-Deoxyacyclovir. 4. Conclusion.