Preparative Electrochemical Reduction of 2-Amino-6-chloropurine and Synthesis of 6-Deoxyacyclovir, a Fluorescent Substrate of Xanthine Oxidase and a Prodrug of Acyclovir.

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Abstract
D.c. polarography of 2-amino-6-chloropurine in aqueous medium over a broad pH range revealed two diffusion waves, the first of which corresponds to reduction of the C(6)-Cl bond, leading to formation of 2-aminopurine in high yield Condensation of the sodium salt of 2-aminopurine with (2-acetoxyethoxy)methyl chloride led to the two isomeric 9- and 7-(2-hydroxyethoxymethyl)-2-aminopurines. The 9- isomer, 6-deoxyacyclovir, a prodrug of acyclovir previously synthesized by another route, was readily converted to the latter by xanthine oxidase: the 7-isomer was not a substrate. The intense fluorescence of 6-deoxyacylclovir makes it a convenient fluorescent substrate for xanthine oxidase, although less sensitive than xanthine; it is shown that 2-aminopurine would be a very sensitive fluorescent substrate. The polarographic behaviour of the riboside of 2-amino-6-chloropurine was virtually identified with that of the parent purine, leading to a simple procedure for conversion of 2-amino-6-chloropurine nucleosides and acyclonucleosides to the corresponding 2-aminopurine congeners.