Cyclization reactions of 1-[3'-hydroxy-2'-(hydroxymethyl)prop-1'-enyl]pyrimidine nucleobases: intramolecular Michael additions to the C(5)=C(6) bonds and intramolecular dehydrations.
The tendency of a series of acyclic nucleoside analogues 1a-f to undergo intramolecular cyclization reactions was investigated. All compounds, when treated with NaOD, were in equilibrium with the bicyclic compounds 2a-f, arising from Michael addition of a hydroxy group to the C(5)=C(6) bonds. Derivatives of 2,4-pyrimidinediones (1a,b) had the highest tendency to undergo intramolecular Michael addition when treated with triethylamine, whereas the cyclization of 4-amino-2-pyridones (1c-f) proceeded best with acid. The exocyclic double bond of was essential for the cyclization to occur. Commonly used N-protecting groups as the benzoyl- and the dibutylaminomethylene group enhanced cyclization. Under acidic anhydrous conditions 1b and 1e cyclized to the 2,4'-anhydro compounds 1b and 1e.
Dahl
Otto
O
Department of Chemistry, University of Copenhagen, The H. C. Ørsted Institute, Universitetsparken 5, DK-2100, Copenhagen, Denmark.
Jensen
Jacob
J
Petersen
Michael Axman
MA
Henriksen
Ulla
U
D003500:Cyclization; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014867:Water / Q000737:chemistry
D011741:Pyrimidine Nucleosides; D014867:Water