SYNTHESIS OF THE 2',3'-DIDEHYDRO-2',3'-DIDEOXY AND 2',3'-DIDEOXY DERIVATIVES OF 6-AZAURIDINE AND A NEW ROUTE TO 2',3'-DIDEHYDRO-2',3'-DIDEOXY-5-CHLOROURIDINE

The 5'-O-(4,4'-dimethoxytrityl) and 5'-O-(tert-butyldimethylsilyl) derivatives of 2',3'-O-thiocarbonyl-6-azauridine and 2',3'-O-thiocarbonyl-5-chlorouridine were synthesized from the parent nucleosides by reaction with 4,4'-dimethoxytrityl chloride and tert-butyldimethylsilyl chloride, respectively, followed by treatment with 1,1'-thiocarbonyldiimidazole. Introduction of a 2', 3'-double bond into the sugar ring by reaction of the 5'-protected 2', 3'-O-thionocarbonates with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine was unsuccessful, but could be accomplished satisfactorily with trimethyl phosphite. Reactions were generally more successful with the 5'-silylated than with the 5'-tritylated nucleosides. Formation of 2',3'-O-thiocarbonyl derivatives proceeded in higher yield with 5'-protected 6-azauridines than with the corresponding 5-chlorouridines because of the propensity of the latter to form 2,2'-anhydro derivatives. In the reaction of 5'-O-(tert-butyl-dimethylsilyl)-2',3'-O-thiocarbonyl-6-azauridine with trimethyl phosphite, introduction of the double bond was accompanied by N3-methylation. However this side reaction was not a problem with 5'-O-(tert-butyldimethylsilyl)-2',3'-O-thiocarbonyl-5-chlorouridine. Treatment of 5'-O-(tert-butyldimethylsilyl)-2',3'-didehydro-2',3'-dideoxy-6-azauridine with tetrabutylammonium fluoride followed by hydrogenation afforded 2',3'-dideoxy-6-azauridine. Deprotection of 5'-O-(tert-butyldimethylsilyl)-2',3'-didehydro-2',3'-dideoxy-5-chlorouridine yielded 2',3'-didehydro-2',3'-dideoxy-5-chlorouridine.