Heterocyclic nucleoside analogues 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has been investigated as a route to heterocyclic nucleoside analogues in which the nucleoside ribose moiety has been replaced by an alternative heterocycle.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.
Adams
D R
DR
Chemistry Department, Heriot-Watt University, Riccarton, Edinburgh, UK.
Boyd
A S
AS
Ferguson
R
R
Grierson
D S
DS
Monneret
C
C
D006571:Heterocyclic Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry*
C114285:1-vinylthymine; D006571:Heterocyclic Compounds; D009705:Nucleosides; D014753:Vinyl Compounds; D013941:Thymine