Functionalization of pyrimidine and purine nucleosides at C4 and C6: C-nucleophilic substitution of their C4- and C6-(1,2,4-triazol-1-yl) derivatives.
A study of C-nucleophilic substitution at the C4-position on pyrimidine and C6-position on 2'-deoxyguanosine to produce novel nucleosides is presented with the spectroscopic properties of their respective substitution products. C4-(1,2,4-triazol-1-yl) pyrimidine nucleosides 1 were treated with nitroalkanes, malononitrile, acetylacetone, ethyl nitroacetate, acetoacetate and cyanoacetate at 100 degrees C in dioxane in the presence of DBU resulting in the production of novel nucleosides 2-11. To explore the application of this methodology to purine chemistry, this approach was used to produce novel analogs from 2'-deoxyguanosine. We found that the triazolo derivative 12 undergoes C-nucleophilic substitution with nitromethane, malononitrile, acetylacetone, ethyl nitroacetate and cyanoacetate in the presence of potassium carbonate (K2CO3) in DMF at 100 degrees C to give novel nucleosides 13-17.
Timoshchuk
Victor
V
TriLink BioTechnologies Inc., San Diego, California, USA. vtimoshchuk@trilinkbiotech.com
D000085:Acetates / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002254:Carbonates / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D009570:Nitriles / Q000737:chemistry; D009595:Nitroparaffins / Q000737:chemistry; D009705:Nucleosides / Q000737:chemistry*; D010422:Pentanones / Q000737:chemistry; D011188:Potassium / Q000737:chemistry; D011684:Purine Nucleosides / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D011741:Pyrimidine Nucleosides / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D013696:Temperature; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D000085:Acetates; D002254:Carbonates; D009570:Nitriles; D009595:Nitroparaffins; D009705:Nucleosides; D010422:Pentanones; D011684:Purine Nucleosides; D011687:Purines; D011741:Pyrimidine Nucleosides; D011743:Pyrimidines; C008790:acetylacetone; C028257:nitroacetic acid; D002244:Carbon; D014508:Urea; C037593:potassium carbonate; C000945:dicyanmethane; D003849:Deoxyguanosine; C483182:N,N'-dibutylurea; D008697:Methane; C008640:nitromethane; D011188:Potassium