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Synthesis of 9‐Halogenated 9‐Deazaguanine N 7 ‐(2′‐Deoxyribonucleosides)
Author(s) -
Seela Frank,
Shaikh Khalil I.,
Wiglenda Thomas,
Leonard Peter
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490224
Subject(s) - chemistry , nucleobase , halogenation , regioselectivity , medicinal chemistry , deoxyribonucleosides , diastereomer , stereochemistry , glycosylation , chloride , n bromosuccinimide , organic chemistry , catalysis , dna , biochemistry , enzyme
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%).