SYNTHESIS OF 1-[CIS-3-(HYDROXYMETHYL)CYCLOBUTYL]-URACIL, 1-[CIS-3-(HYDROXYMETHYL)CYCLOBUTYL]-THYMINE AND 1-[CIS-3-(HYDROXYMETHYL)CYCLOBUTYL]-CYTOSINE

4-(Benzylsulfanyl)pyrimidin-2(1H)-one 6a is prepared from 1-benzoylura cil 10a in three steps and in satisfactory overall yield. Reproducible conditions are found for the cycloaddition reaction between allyl ben zyl ether and dichloroketene, leading to the cyclobutanone derivative 17 in good yield. trans-3-(Benzyloxymethyl)cyclobutan-1-ol 15 reacts u nder standard Mitsunobu conditions with the pyrimidine derivative 6a o n O-2 to give compound 20, which is converted into s-3-(hydroxymethyl) cyclobutoxy]pyrimidin-4(3H)-one 24 in good overall yield. Under the sa me Mitsunobu conditions, 3-benzoyluracil 11a and 3-benzoylthymine 11b react with the trans-alcohol 15 on N-1 to give their 1-[cis-3-(benzylo xymethyl)cyclobutyl] derivatives 27a and 27b, respectively. The latter compounds 27a and 27b are converted into 1-[cis-3-hydroxymethyl)cyclo butyl]uracil 13a and 1-[cis-3-(hydroxymethyl)cyclobutyl]thymine 13b in satisfactory overall yields. The uracil derivative 13a is converted i nto 1-[cis-3-(hydroxymethyl)cyclobutyl]cytosine 14 in good yield.