Antiviral and Antineoplastic Pyrimidines

The nuleotide, uridine (43-1), provides the starting material for one of these agents. Treatment of that compound with mercuric chloride leads to the mercuration 

A significantly different strategy is used in the preparation of the corresponding uridine derivative that retains a double bond in the sugar-like moiety. One of the 

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

The isostere in which sulfur replaces the methylene group at the 4 position in the furan ring of customary sugars also shows good activity as an inhibitor of HIV reverse transcriptase. The initial step consists of formation of the thioacetal (53-3) from glyoxal benzoate (53-1) and the methyl acetal of thioglyoxal (53-2). Reaction of 

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