NUCLEOSIDES .61. TRANSFORMATIONS OF PYRIMIDINE NUCLEOSIDES IN ALKALINE MEDIA .4. CONVERSION OF 5-HYDROXYURIDINES INTO IMIDAZOLINE NUCLEOSIDES

Isopropylidene-5-hydroxyuridine (2) and 1-methyl-5-hydroxyuracil (8) undergo a benzilic acid type of rearrangement and dehydration in 0.1 N NaOH at 100° to give the corresponding 1-substituted 2-oxo-4-imidazoline-4-carboxylic acids 5 and 9. 1,3-Dimethyl-5-hydroxyuracil (10a) and 1-methyI-3-benzyl-5-hydroxyuracil (10b) are converted under these conditions into the corresponding 1,3-disubstituted 4-hydroxy-2-oxoimidazolidine-4-carboxylic acids 11a and b. Compound 11b was converted into the crystalline methyl ester 14 by treatment with diazomethane. The 4-hydroxyimidazolidines 11a and b undergo acid-catalyzed dehydration to give the 1,3-disubstituted 2-oxo-4-imidazoline-4-carboxylic acids 12a and b. Evidence for the existence of the tautomeric 5-keto forms of the 5-hydroxyuracil derivatives necessary for benzilic acid rearrangement is presented. The 5-hydroxyuracil derivatives are prepared by treatment of the corresponding 5-bromouracils with CO2-buffered sodium bicarbonate solution at 100°. In unbuffered sodium bicarbonate solution, isopropylidene-5-bromouridine (1) and 2ʹ-deoxy-5-bromouridine are converted via their 5-hydroxy derivatives into the 2-oxo-4-imidazoline-4-carboxylic acid nucleosides. The potential application of this rearrangement to DNAs containing 2ʹ-deoxy-5-bromouridine instead of thymidine is discussed. An in situ method for the conversion of uridine into the imidazoline nucleoside 6 is described. Ultraviolet spectral and pKa data for the 5-hydroxyuracil derivatives are given. © 1969, American Chemical Society. All rights reserved.