2-Amino-6-(4-chlorophenyltNo)-(2,3,5-tri-O-acetyl-B-pribofuranosyl)purine 11. which is readily prepsred by allowing the corresponding 6chloro-compound 10 to react with 4-chloro(thiopheno1) and triethylamine in methanol solution at rooa temperature, reacts with boron trifluoride diethyl etherateinboilingdichloromethane solution to give2-aaino-6-(4-chlorophenylthio)-9H-purine 12 in hi& isolated yield. 9-[(2-Acetoxyethoxy)methyl]-2amino-6-(4-chlorophenylthio)~9ZGpurine 13. prepared froa the latter sglycone 12 in good yield, is converted by a four-step process into acyclovir 1 and by a two-step process into 6-deoxyacyclovir 2.
A nuaber of nucleoside analogues in which the sugar residues have been replaced by acyclic side-chains have been found to possess high sntiviral activity'. A particularly notable group of such analogues which have either already found or are likely to find application in cheaotherapy are achiral 9-alkylguanine or closely related 9-alkyl-2aainopurine derivatives. This group of coapounds includes acyclovir2 1, its 6-deoxy-derivative3 2. ganciclovir4 3. penciclovir5 4 and faaciclovir6 5. A possible overall strategy for the synthesis of these and indeed other related alkylated purines consists essentially of two main parts. The first such part involves the preparation of s purine derivative that undergoes alkylation highly regioselectively (or preferably regiospecifically) on N-9. and is so designed that the resulting alkylation product can readily be converted into the corresponds 9-alkylguanine or 9-alkyl-2-aainopurine. The other main part involves the preparation of the synthons required for the introduction of the appropriate acyclic side-chains. The preaent study has been directed towards the first part of the overall strategy, that is the synthesis of a suitable purine derivative. The possible utility of the purine derivative aelected (aee 12 below) is illustrated by its conversion into both acyclovir 1 and the corresponding prodrug 6-deoxyacyclovir 2.