ViaSynthesis of Purine Acyclonucleosides Ribofuranose-Ring Cleavage of Purine Nucleosides By Diisobutylaluminum Hydride

Abstract

Among nucleoside analogs, acyclonucleosides such as acyclovir and ganciclovir have been developed for the treatment of certain herpes virus infections. The discovery of acyclovir has stimulated extensive research in the synthesis of new acyclonucleosides in which the carbohydrate moieties are acyclic chains mimicking the sugar portion of naturally occurring nucleosides. Most synthetic methods for the preparation of such acyclonucleosides involve the condensation of the base moiety with the appropriate side chain moiety. Synthetic methods starting from commercially available nucleosides such as adenosine and guanosine have been unprecedent except for an example of oxidative cleavage of the 2',3'-cis-diol portion of ribonuculeosides with NaIO4. A study on the synthesis of 1,6-dihydropurine nucleosides using various reducing agents, it was found that reduction of purine nucleosides with diisobutylaluminum hydride (DIBAL-H) caused a selective cleavage of the C-1’–O-4’ bond in the ribose ring to give the corresponding 9-D-ribitylpurines. The scope and limitation of this methodology for the synthesis of 9-D-ribitylpurines and the application to the synthesis of acyclic nucleoside are described in the chapter.