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}-...

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Bibliographic Details
Published inHelvetica chimica acta Vol. 87; no. 10; pp. 2507 - 2516
Main Authors Seela, F, Shaikh, KI, Wiglenda, T, Leonard, P
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 01.10.2004
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
OLIGONUCLEOTIDE DUPLEXES
SUGAR CONFORMATION
PURINE NUCLEOSIDE PHOSPHORYLASE
DNA
STABILITY
SUBSTITUENTS
TRIPLE-HELIX FORMATION
INHIBITORS
DERIVATIVES
STRUCTURE-BASED DESIGN
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Summary: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]-4H-pyrrolo[3,2-d]pyrimidin-4-one). Nucleobase-anion glycosylation of 4a-c with 2-deoxy-3,5-di-O-(p-toluoyl)-alpha-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%).
ISSN:0018-019X
1522-2675
DOI:10.1002/hlca.200490224