Preparative electrochemical reduction of 2-amino-6-chloropurine and synthesis of 6-deoxyacyclovir, a fluorescent substrate of xanthine oxidase and a prodrug of acyclovir.
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-deoxyacyclovir 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 identical 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.
Kusmierek
J T
JT
Institute of Biochemistry and Biophysics, Academy of Sciences, Warszawa, Poland.
Czochralska
B
B
Johansson
N G
NG
Shugar
D
D
D015075:2-Aminopurine / Q000031:analogs & derivatives*; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D004572:Electrolysis; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000188:drug therapy; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011048:Polarography; D011355:Prodrugs / Q000138:chemical synthesis; D018139:Simplexvirus / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D010948:Viral Plaque Assay; D014969:Xanthine Oxidase / Q000378:metabolism
D000998:Antiviral Agents; D011355:Prodrugs; D015075:2-Aminopurine; C040510:2-amino-6-chloropurine; C041468:desciclovir; D014969:Xanthine Oxidase; D000225:Adenine; D000212:Acyclovir