NUCLEOSIDES .58. TRANSFORMATIONS OF PYRIMIDINE NUCLEOSIDES IN ALKALINE MEDIA .3. CONVERSION OF 5-HALOGENOURIDINES INTO IMIDAZOLINE AND BARBITURIC ACID NUCLEOSIDES

Reaction of 2ʹ,3ʹ-0-isopropylidene-5-bromouridine (3b) with alkoxide affords 5ʹ,6-anhydro-2ʹ,3ʹ-0-isopropylidene-6-hydroxyuridine (15) which is converted by acid hydrolysis into 1-β-D-ribofuranosylbarbituric acid (“6-hydroxyuridine”) (18) in high over-all yield. Treatment of 15 with NaOBz-DMF gives the 5ʹ-O-benzoate of isopropylidene-6-hydroxyuridine (19). In aqueous alkali, 2ʹ,3ʹ-o-isopropylidene-5-fluorouridine (3a) is converted into 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2-oxo-4-imidazoline-4-carboxylic acid (20) which, after acid hydrolysis, gives the unblocked imidazoline ribo nucleoside (2) in good over-all yield. A total synthesis of 2 via condensation of methyl 2-oxo-4-imidazoline-4-carboxylate with tri-O-benzoyl-D-ribofuranosyl chloride is given. Unlike the 5-fluoro derivative (3a), the 5-bromo (3b) and the 5-iodo (3c) analogs in aqueous alkali give poor yields of 20 along with other 2ʹ,3ʹ-O-isopropylidenated products, namely, 5ʹ,6-anhydro nucleoside (15), uridine (12), 5-hydroxyuridine (17), and barbituric acid ribo nucleoside (13). It is shown that the conversion of nucleosides 3 into 12, 17, and 20 involves anchimeric assistance by the 5-hydroxyl group of the sugar moiety and, further, that the presence of a 2ʹ,3ʹ-O-isopropylidene group promotes this participation. Evidence obtained from a study of the 5ʹ-deoxy analog (9b) of 3b suggests that the formation of 13 from 3b or 3c occurs mainly by direct attack by hydroxide ion on C-6 and to a lesser extent by solvolysis of 15. © 1969, American Chemical Society. All rights reserved.