Article

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

Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastrasse 7, D-49069 Osnabrück and Center for Nanotechnology (CeNTech), Gievenbecker Weg 11, D-48149 Münster (phone: +49-(0)541-969-2791; fax: +49-(0)541-969-2370)
Helvetica Chimica Acta (Impact Factor: 1.38). 09/2004; 87(10):2507 - 2516. DOI: 10.1002/hlca.200490224

ABSTRACT The syntheses of N7-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]-4H-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 0.01M 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. NH3 solution furnished the nucleosides 1a–c. In D2O, the sugar conformation was always biased towards S (67–61%).

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