Synthesis of Cytosine Radiolysis Products: Cis- and trans-1-Carbamoyl-4,5-dihydroxyimidazolidin-2-one

Abstract

The cytosine γ-radiolysis products cis- and trans-1-carbamoyl-4,5-dihydroxyimidazolidin-2-one (1, 2 as racemic modifications) have been synthesized from a common precursor, 1-carbamoyl-4-imidazolin-2-one (3). Oxidation of 3 with OsO4 in aqueous pyridine provided the intermediate cis-1-carbamoyl-4,5-dihydroxyimidazolidin-2-one bis(pyridine) cyclic osmate (8) which, upon reductive hydrolysis with aqueous NaHSO3, followed by continuous extraction with EtOAc, gave the trans isomer 2. Treatment of 3 with OsO4 in dry DMF, followed by reductive cleavage with H2S, provided the pure cis isomer 1. The structure of the cis isomer was confirmed by observing (by NMR) its conversion to 8 upon treatment with Os2O6·py4. The assignment of 1H NMR chemical shifts and coupling constants for the intermediates and products were confirmed in part by examination of additional synthetic models: 2-N-methylcarbamoyl-4-imidazolin-2-one, 1-N,N-dimethylcarbamoy-4-imidazolin-2-one, and 1-methyl-4-imidazolin-2-one. © 1976, American Chemical Society. All rights reserved.