Synthesis of 9‐Halogenated 9‐Deazaguanine N⁷‐(2′‐Deoxyribonucleosides).

Abstract

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 4aNucleobase-anion glycosylation of 4a ± c with 2-deoxy-3,5-di-O-(p-toluoyl)-a-d-erythro-pentofuranosyl chloride (5) furnished the fully protected intermediates 6a ± c (Scheme 2). They were deprotected with 0.01m NaOMe yielding the sugar-deprotected derivatives 8a ± c (Scheme 3). At higher concentrations (0.1m 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%).