Pyrimidine nucleosides. Part II. The direct glycosidation of 2,6-di-substituted 4-pyrimidones

Journal of the Chemical Society C: Organic Pub Date: DOI: 10.1039/J39690000791

Abstract

The first successful direct N-glycosidation of a 2,4,6-trisubstituted pyrimidine containing hydroxy- and/or aminogroups at all three positions has now been achieved. Use of the silylation and alkylation procedure has resulted in above 70% yield of 6-amino-3-(β-D-ribofuranosyl)pyrimidine-2,4-dione (10)[6-hydroxycytidine (11)]. Barbituric acid under similar treatment gives ca. 60% yield of 1-(β-D-ribofuranosyl)barbituric acid (1)(6-hydroxyuridine). 6-(Methylthio)uracil (2) likewise gave above 70% yield of 6-methylthio-3-(β-D-ribofuranosyl)-pyrimidine-2,4-dione (6). Conversion of (6) into 3-(β-D-ribofuranosyl)uracil, an isomer of uridine, was readily accomplished with Raney nickel. Attempts to employ 4-amino-6-hydroxypyrimidine-2-thione directly in this reaction resulted in an S-glycoside. This method of pyrimidine nucleoside formation appears to be superior to older coupling procedures which have failed with 6-aminouracil and barbituric acid. The exceptionally good yields and the simplicity of the procedure suggest that this method deserves further study.

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