Synthesis of pyrimidine and purine nucleosides

Abstract

Amino-nucleic acids and amino-heterocycles reacted readily with tbuthylthionitrate or t-buthylthion itrate in the presence of anhydrous sodium tetrafluoroborate in neutral and aprotic media to afford the corresponding fluoronucleic acids and fluoro-heterocycles respectively in good yields. 1-(Tetrahydro-2-furyl) pyrimidine and 9-(tetrahydro-2-furyl) purine derivatives were successfully synthesized in good yields by the reaction of trimethylsilylated pyrimidine and purine bases with 2-acetoxytetrahydrofuran using a new catalyst of cesium chloride in acetonitrile under mild conditions. N3-Methylated purine acyclic nucleosides as analogues of acyclovir were newly synthesized from imidazole precursors so that structureactivity relationships in this area could be explored. 4,5-Dicyanoimidazole was alkylated and then the 5-cyano group was converted to amino group by Hofmann rearrangement reaction to afford the corresponding 1-substituted-5-amino-4-imidazolecarbonitriles as the important precursors for the synthesis of purine nucleosides. Reaction of 6-amino-1,3-dimethyluracil with benzoylisothiocyanate or ethoxycarbonylisothiocyanate afforded the corresponding thioureido derivatives and then subsequently treated with hydroxylamine to afford the 8-aminoxantines respectively. 6-Amono-2-mercaptopurine was silylated, condensed with peracylated sugar and selectively methylated at N1-position to give N1-methyl-2-thioadenosine as a sulfur analogue of doridosine. Electrophilic additions of phenylsulfenyl chloride or phenylselenenyl chloride to a carbon-carbon double bond of c-5,6 region of uracils in the presence of silver reagents directly gave the corresponding 5-phenylsulfydryl-or 5-phenylselenenyl uracils in good yields. The 5-phenylselenenyluracils were investigated for the modification of pyrimidine base through the various transformations due to some unique properties of organic-seleno group.