HETEROCYCLIC NUCLEOSIDE ANALOGS BY CYCLOADDITION REACTIONS OF 1-VINYLTHYMINE WITH 1,3-DIPOLES

1,3-Dipolar cycloaddition of 1-vinylthymine to azides, nitrile oxides, nitrones and nitronates has been investigated as a route to heterocyc lic nucleoside analogues in which the nucleoside ribose moiety has bee n replaced by an alternative heterocycle. Reaction of 1-vinylthymine w ith highly reactive nitrile oxides affords 1(isoxazolin-5-yl)thymine p roducts in excellent yield at room temperature. The less reactive nitr one dipoles undergo cycloaddition to 1-vinylthymine at elevated temper ature to afford 1-(isoxazolidin-5-yl)thymine cycloadducts in good-to-m oderate yields, but show a tendency to eliminate thymine from the cycl oaddition products over long reaction times. Azide cycloadditions to 1 -vinylthymine proceed only under forcing conditions to which the fragi le triazoline products are unstable.