1,3-Dipolar cycloaddition of 1-vinylthymine to azides, nitrile oxides, nitrones and nitronates has been investigated as a route to heterocyclic nucleoside analogues in which the nucleoside ribose moiety has been replaced by an alternative heterocycle. Reaction of 1-vinylthymine with highly reactive nitrile oxides affords 1(isoxazolin-5-yl)thymine products in excellent yield at room temperature. The less reactive nitrone dipoles undergo cycloaddition to 1-vinylthymine at elevated temperature to afford 1- (isoxazolidin-5-yl)thymine cycloadducts in good-to-moderate yields, but show a tendency to eliminate thymine from the cycloaddition products over long reaction times. Azide cycloadditions to 1-vinylthymine proceed only under forcing conditions to which the fragile triazoline products are unstable.
|Number of pages||23|
|Journal||Nucleosides and Nucleotides|
|Publication status||Published - 1998|