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

Abstract

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 1 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 3b and 3e.