Syntheses of Pyrimidine Nucleosides

It was generally conceded139-179 that glycosylation at N1 of the pyrimidine ring is not a feasible approach where lactam-lactim tautomerism of the OH OH 

The authors suggested that the intermediate addition product (XLV not isolated) might be very unstable. Even when much less than one molar proportion of alkyl halide was used in this reaction, complete transformation of XLIV to XLVI was 

6-dihydro derivative which was readily cleaved by dilute acid to 5,6-dihydrouracil plus D-glucose.139 Confirmation of the l-/J-D-pyranosyl structure assigned to XLIX and L has already been discussed (see p. 314). 

By use of the Hilbert-Johnson procedure,139,140 a synthesis186 of cytidine (II) was effected this involved condensation of crude tri-O-acetyl-D-ribo-furanosyl bromide with a 2,4-dialkoxypyrimidine, followed by treatment of the crude reaction mixture with alcoholic ammonia. Although the yields were low, this achievement marked the first synthesis of a naturally occurring nucleoside. 

Aside from the successful synthesis of cytidine,185 attempts made thus far to apply the Hilbert reaction to the preparation of 1 -glycofuranosyl-pyrimidines have yielded anomalous results. Although the syntheses of 5 -methyluridine (I, R = CH3) and 5 -methylcytidine (II, R = CH3) by the condensation of sirupy tri-O-acetyl-D-ribofuranosyl bromide with 2,4-diethoxypyrimidine have been reported,192 the properties of these nucleosides differ from those of the verified substances synthesized by other routes.68 62 Other aspects of the Hilbert-Johnson procedure are discussed below. 

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