9-deazapurine nucleosides. The synthesis of certain N-5-2′-deoxy-β-D-erythropentofuranosyl and N-5-β-D-arabinofuranosylpyrrolo[3,2-d]pyrimidines

A number of 2,4-disubstituted pyrrolo[3,2-d]pyrimidine N-5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (3) using 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythropentofuranose (1) and 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose (11) . The resulting N-5 glycosides, 2,4-dichloro-5-(2-deoxy-3,5-di-O-(p-toluoyl) -β-D-erythropentofuranosyl)-5H-pyrrolo-[3,2-d]pyrimidine (4) and 2,4-dichloro-5-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl-5H -pyrrolo [3,2-d)pyrimidine (12) , served as versatile key intermediates from which the N-7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4-amino-5-(2-deoxyerythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidine (6) . Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (9) . Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2-amino-5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (10) . The preparation of the same analogs in the β-D-arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′-deoxy-β-D-ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene-palladium hydroxide on carbon, providing 4-amino-5-β-D-arabinofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (18) . Structural characterization of the 2′-deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single-crystal X-ray analysis of 15a . The stereospecific attachment of the 2-deoxy-β-D-ribofuranosyl and β-D-arabinofuranosyl moieties appears to be due to a Walden inversion at the C₁ carbon by the anionic heterocyclic nitrogen (S_N2 mechanism).