6-Bromopurine nucleosides as reagents for nucleoside analogue synthesis

E. A. Véliz, P. A. Beal

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Surprisingly facile direct substitution reactions with acetyl-protected 6-bromopurine nucleosides are described. Included in the series of bromonucleosides studied is the guanosine derivative N2-2′,3′,5′-tetraacetyl-6-bromopurine ribonucleoside, the synthesis of which is reported here for the first time. Brominated nucleosides had not previously been considered optimal substrates for SNAr reactions given the general reactivity trend for halogenated aromatic systems (i.e. F > Cl > Br > I). However, even weakly nucleophilic aromatic amines give high yields of the substitution products in polar solvents with these 6-bromopurine nucleosides. For primary aromatic amines, secondary aliphatic amines, and imidazole, reaction takes place only at C6, with no effect on the acetyl-protected ribose. In addition, we report the first synthesis of 3′,5′-di-O-acetyl-6-bromopurine-2′-deoxyribonucleoside and its reaction with an arylamine in MeOH in the absence of added metal catalyst. Thus, C6-arylamine derivatives of both adenosine and 2′-deoxyadenosine can be prepared via simple SNAr reactions with the corresponding 6-bromo precursor. We also describe high yielding and C6-selective substitution reactions with 6-bromonucleosides using alcohol and thiol nucleophiles in the presence of added base (DBU). Finally, C6-bromonucleosides are shown to be readily hydrogenated to give purine or 2-aminopurine products in good yield. This work increases the arsenal of reactions and strategies available for the synthesis of nucleoside analogues as potential biochemical tools or new therapeutics.

Original languageEnglish (US)
Pages (from-to)8592-8598
Number of pages7
JournalJournal of Organic Chemistry
Volume66
Issue number25
DOIs
StatePublished - Dec 14 2001
Externally publishedYes

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Nucleosides
Amines
Substitution reactions
2-Aminopurine
Deoxyribonucleosides
Arsenals
Derivatives
Ribonucleosides
Nucleophiles
Ribose
Guanosine
Sulfhydryl Compounds
Adenosine
Metals
Alcohols
Catalysts
Substrates

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

6-Bromopurine nucleosides as reagents for nucleoside analogue synthesis. / Véliz, E. A.; Beal, P. A.

In: Journal of Organic Chemistry, Vol. 66, No. 25, 14.12.2001, p. 8592-8598.

Research output: Contribution to journalArticle

Véliz, E. A. ; Beal, P. A. / 6-Bromopurine nucleosides as reagents for nucleoside analogue synthesis. In: Journal of Organic Chemistry. 2001 ; Vol. 66, No. 25. pp. 8592-8598.
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