Synthesis of 9-[cis-3-(hydroxymethyl)cyclobutyl]-adenine and -guanine

Abstract

2,2-Dichloro-3-(benzyloxymethyl)cyclobutanone 15, which was prepared in 50% yield by the cycloaddition of dichloroketene to allyl benzyl ether 14, was converted in four steps and in ∼ 40% overall yield into trans-3-(benzyloxymethyl)cyclobutanol 11b. The latter alcohol 11b was coupled under Mitsunobu conditions with 6-(4-chlorophenylsulfanyl)-9H-purine 21b and 6-(4-chlorophenylsulfanyl)-2-(phenylacetamido)-9H-purine 21c to give the 9-cyclobutylpurine derivatives 22 and 24, respectively, in 88 and 60% yield. The former product 22 was converted in three steps and in 39% overall yield into 9-[cis-3-(hydroxymethyl)cyclobutyl]adenine 6, and the latter product was converted in four steps and in 42% overall yield into 9-[cis-3-(hydroxymethyl)cyclobutyl]guanine 7. X-Ray crystallographic data relating to compounds 22 and 24 are also reported.