2-Pyrimidinone, pyrimidine nucleoside

The iodination of pyrimidines requires the presence of an activating substituent, and is normally performed with reagents such as A -iodosuccinimide (NI8) or iodine monochloride (ICl). A microwave-assisted procedure for the rapid and high-yielding C-5 iodination of substituted pyrimidinones and pyrimidine nucleosides with NIS in dimethylfor-mamide (DMF) has been developed, and thus the iodination of uracil occurred in 98% yield with just 3 min reaction time <200381039>. 

Identification of the nitrogenous bases (aglycons) of pyrimidine nucleosides began at the turn of the century, when Kossel and Neumann18 isolated thymine (5-methyluracil) from nucleic acid and showed this pyrimidine to be identical with the nucleosin previously described by Miescher.19 The isolation of cytosine20 [4-amino-2()//)-pyrimidinone] and uracil21 [2,4(1, 3 )-pyrimidinedione] from the nucleic acids came shortly there-... 

N-Alkylation in the azine ring is demonstrated by the preparation of 2-substituted 6-(jS-D-ribofuranosyl)oxazolo[5,4-rf]pyrimidin-7(6/T)-ones (181). In this case the silyl ether variant of the Hilbert-Johnson method for the synthesis of pyrimidine nucleosides has been used the pyrimidinone (180) is converted into its silyl ether using HMDS and the ether reacted with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide under Hg(II) catalysis. Deacetylation using methanolic ammonia gives the nucleoside with a /3-anomeric configuration (74JMC1282). 

The synthesis of corresponding pyrimidine nucleosides was not possible by the mercuric chloride method. The syntheses succeeded, however, on application of the Hilbert—Johnson procedure. Tetra-O-acetyl-4-thio-D-ribofuranose was transformed with ethereal hydrogen chloride into the glycosyl chloride derivative 254, and this was directly heated for five days with 2,4-diethoxy-5-methylpyrimidine. The anomeric forms of 4-ethoxy-5-methyl-l-(2,3,5-tri-0-acetyl-4-thio-D-ribofuranosyl)-2(lH)-pyrimidinone obtained could be separated... 

In synthesis of pyrimidine nucleosides, the mercuripyrimidine method was ei for the preparation of 6-methyl and 5,6-dimethyl uridines andcytidines, 2-thiouridine and 2-thiocytidine (from the S-acetyl pyrimidines), as well as D-ribosides of 4-pyri midi none 2-pyrimidinone, and 4,6-pyrimidirtedione. In... 

Figure 3. Proposed mechanism of pyrimidine nucleoside formation, a) Structures of the pyrimidine bases uracil, cytosine, and 2-pyrimidinone. Uracil and cytosine are protonated at N1 and therefore do not possess an in-plane lone pair of electrons, whereas 2-pyrimidinone does, b) The lone pair on 2-pyrimidinone nucleophilically attacks Cl of the oxonium sugar intermediate to form the glycosidic bond.

By far the most important naturally occurring diazines are the pyrimidinones uracil, thymine and cytosine, which, as the nucleosides uridine, thymidine and cytidine, are components of the nucleic acids, and as a consequence, a great deal of synthetic chemistry has been directed towards these types of compound in the medicinal context (33.6.3 and 33.7). (In this chapter, the designations 4-pyrimidinone and pyrimidin-... 

Nucleosides in the j-triazolo[2,3- ]-5-pyrimidinone and 5-triazolo[4,3-a]-7-pyrimidinone series have been synthesized by way of silyl or fusion procedures. The former procedure afforded the kinetically favoured product (354) substituted in the triazole ring, whereas the fusion procedure yielded the thermodynamically favoured product (355) substituted in the pyrimidine ring. 

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