Synthesis Of Novel C6 Modified Purine Nucleoside Derivetives

Nucleosides, as significant constitution unit of nucleic acid, participate the course of reservation, copy, conversation of genes. And the nucleoside derivatives, which has similar structure with nucleosides, can act as nucleic acid metabolic inhibitor to interfere with the development of tumor cell and the multiplication of virus. By now, thousands of nucleoside derivatives have been synthesized and many of them have been used in clinic as anti-tumor or anti-virus drugs.In order to superinduce the structural type and find original active compounds, 7-β-D-ribofuranosyl-7H-1,2,4-triazolo[3,4-i]purine derivatives and 6-alkyloxy-amino -purine derivatives were designed and their synthetic methods were studied. Finally many new compounds of the target type were achieved.The synthesis of 7-β-D-ribofuranosyl-7H-1,2,4-triazolo[3,4-i]purine derivatives start from 6-hydroxy-purine nucleoside and include glycosylation, chlorination, deprotection of the hydroxyl group in the ribose, nucleophilic substitution of the hydrazine, condensation with aldehyde or ketone, and the last one, oxidative cyclization. As a key step, the oxidative cyclization of the corresponding hydrazone to form the 1,2,4-triazolo[3,4-i]purine required an optimization of methodology to obtain the desired conversion. Specifically, a new oxidation reagent was applied to this reaction and a mechanism for the transformation was proposed. This new method provides a rapid, productive, and simple synthesis of the desired product under mild conditions.In the synthesis of 6-alkyloxy-amino-purine derivatives, the C6 position was designed to be substituted by a variety of alkoxylamines. In this research, some catalysts were researched to enhance the reactivity of replacement at the C6 position of purine nucleosides by the weak nucleophilic alkoxylamines and finally the desired compounds were obtained.