Preparation of the 2′-Deoxynucleosides of 2,6-Diaminopurine and Isoguanine by Direct Glycosylation

Abstract

The purine nucleoside 2,6-diaminopurine-2'-deoxyriboside is prepared by the direct glycosylation of the 2,6-bis(tetramethylsuccinimide) derivative of the parent purine heterocycle 4 with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-D-erythro-pentofuranosyl chloride 5 using the sodium salt method. 2'-Deoxyisoguanosine is prepared from 2,6-diaminopurine by a five-step procedure. The purine heterocycle isoguanine is prepared by selective diazotization of 2,6-diaminopurine and then converted to the N9-trityl derivative to increase solubility. After silylation of the O(2)-carbonyl with TMSCl, the N(6)-amino group is protected as the tetramethylsuccinimide (M(4)SI). The O(2)-carbonyl is protected as the DPC derivative, and the trityl group is removed. The resulting product is glycosylated in good yield to generate fully protected 2'-deoxyisoguanosine.