Synthesis of 9‐Halogenated 9‐Deazaguanine N 7 ‐(2′‐Deoxyribonucleosides)

The syntheses of N 7 ‐glycosylated 9‐deazaguanine 1a as well as of its 9‐bromo and 9‐iodo derivatives 1b , c are described. The regioselective 9‐halogenation with N ‐bromosuccinimide (NBS) and N ‐iodosuccinimide (NIS) was accomplished at the protected nucleobase 4a (2‐{[(dimethylamino)methylidene]amino}‐3,5‐dihydro‐3‐[(pivaloyloxy)methyl]‐4 H ‐pyrrolo[3,2‐ d ]pyrimidin‐4‐one). Nucleobase‐anion glycosylation of 4a – c with 2‐deoxy‐3,5‐di‐ O ‐( p ‐toluoyl)‐α‐ D ‐ erythro ‐pentofuranosyl chloride ( 5 ) furnished the fully protected intermediates 6a – c ( Scheme 2 ). They were deprotected with 0.01 M NaOMe yielding the sugar‐deprotected derivatives 8a – c ( Scheme 3 ). At higher concentrations (0.1 M NaOMe), also the pivaloyloxymethyl group was removed to give 7a – c , while conc. aq. NH 3 solution furnished the nucleosides 1a – c . In D 2 O, the sugar conformation was always biased towards S (67–61%).