The synthesis and properties of new carbohydrate-modified mesoionic thiazolo[3,2-a]pyrimidine-5,7-dione acyclonucleosides

The synthesis of the first examples of Class II mesoionic thiazolopyrimidine acyclonucleosides (MTA) incorporating the 2,3-dihydroxypropyl moiety as the sugar simulator is described. First, 2-bromothiazole was reacted with excess 1-amino-2,3-propanediol acetonide via an aromatic nucleophilic substitution reaction to yield 1-(2-thiazolylamino)-2,3-propanediol acetonide. This acetonide intermediate was condensed at 160degrees with substituted bis(2,4,6-trichlorophenyl) malonic esters to form a series of protected acyclonucleosides termed anhydro-(8-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-hydroxy-7-oxothiazolo[3,2-a]pyrimidinium hydroxides) which differ in their 6-position substituent. Deprotection of these acyclonucleosides using p-toluenesulfonic acid catalyst in methanol at 65degrees yielded the desired Class II MTA, anhydro-(8-(2,3-dihydroxypropyl)-5-hydroxy-7-oxothiazolo[3,2-a]pyrimidinium hydroxides).