Inhibitory Effects of the Guanine Moiety on Suzuki Couplings of Unprotected Halonucleosides in Aqueous Media
| Autor: | Kevin H. Shaughnessy, Elizabeth C. Western |
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| Rok vydání: | 2005 |
| Předmět: |
Anions
Chromatography Gas Guanine Magnetic Resonance Spectroscopy Phosphines Stereochemistry Induction period chemistry.chemical_element Ligands Medicinal chemistry chemistry.chemical_compound Deprotonation Suzuki reaction Moiety Chromatography High Pressure Liquid Aqueous solution Molecular Structure Chemistry Organic Chemistry Temperature Water Nucleosides Nuclear magnetic resonance spectroscopy Hydrogen-Ion Concentration Solubility Palladium |
| Zdroj: | The Journal of Organic Chemistry. 70:6378-6388 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/jo050832l |
| Popis: | In the Suzuki arylations of unprotected halonucleosides in aqueous media, 8-bromo-2'-deoxyguanosine (8BrdG) couplings were slower to reach completion than the corresponding 8-bromo-2'-deoxyadenosine (8BrdA) couplings. The guanine moiety has an acidic proton, which under our Suzuki conditions (pH congruent with 10) may be deprotonated to give an anion that can coordinate to palladium. The possibility that guanine coordination was responsible for the observed slower rates was explored using additive experiments in which nonhalogenated nucleosides were added to the Suzuki coupling reaction of 8BrdA or 4-bromotoluene and PhB(OH)2 and the reaction progress monitored by HPLC or GC. Adding dG slowed these reactions, and an induction period was observed. The addition of dA or 1-methyl-2'-deoxyguanosine (1MedG) to these couplings did not affect the rate of conversion to product. Guanine coordination was further explored using 13C and 31P NMR spectroscopy, which implies that guanine is coordinating to palladium through N-1 or O-6, or both. Furthermore, the presence of dG inhibited the formation of the active palladium(0) catalytic species, which may account for both the observed induction period and the sluggishness of reactions where guanine is involved. |
| Databáze: | OpenAIRE |
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