A novel synthesis of acyclonucleosides via allylation of 3-[1-(phenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one.
The allylation of 3-[1-(phenylhydrazono)-L-threo-2,3,4-trihydroxybut-1-yl]quinoxalin-2(1H)one (1) gave, in addition to the anticipated 1-N-allyl derivative (2), a dehydrative cyclized product, 1-N-allyl-3-[5-(hydroxymethyl)-1-phenylpyrazol-3-yl]quinoxalin-2-one (4) and its isomeric O-allyl derivative 3. The O-allyl group in 3 underwent acetolysis under acetylation conditions, in addition to the acetylation of the hydroxyl group, to afford 2-acetoxy-3-[5-(acetoxymethyl)-1-phenylpyrazol-3-yl]quinoxaline (8) instead of the O-acetyl derivative of 3. Allylation of the tri-O-acetyl derivative of 1 caused the elimination of a molecule of acetic acid in addition to N-allylation to give 1-N-allyl-3-[3,4-di-O-acetyl-2-deoxy-1-(phenylhydrazono)but-2-en-1-yl]quinoxalin-2-one (11). Hydroxylation of the allyl group gave a glycerol-1-yl acyclonucleoside which can be alternatively obtained by a displacement reaction of the tosyloxy group in 2,3-O-isopropylidene-1-O-(p-tolylsulfonyl)glycerol (14), followed by deisopropylidenation. 1-N-(2,3-Dibromopropyl)-3-[5-(hydroxymethyl)-1-(4-bromophenyl)pyrazol-3-yl]quinoxalin-2-one (15) underwent azidolysis to give a 2,3-diazido derivative. The assigned structures were based on spectral analysis. The activity of compounds 2, 4, 6, and 15 against hepatitis B virus was studied.
Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt. habdelhamid3@yahoo.com
Hamida Mohamed Abdel
HM
Hamid
D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D016133:Polymerase Chain Reaction; D011810:Quinoxalines / Q000737:chemistry*
C487456:3-(1-(phenylhydrazono)-2,3,4-trihydroxybut-1-yl)quinoxalin-2-(1H)-one; D006835:Hydrazones; D009705:Nucleosides; D011810:Quinoxalines