Synthesis of 9‐Halogenated 9‐Deazaguanine N7‐(2′‐Deoxyribonucleosides) |
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Authors: | Frank Seela,Khalil I. Shaikh,Thomas Wiglenda,Peter Leonard |
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Affiliation: | Frank Seela,Khalil I. Shaikh,Thomas Wiglenda,Peter Leonard |
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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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