Synthesis and evaluation of acyclic sugar nucleosides.
Acylated aldose dialkyl dithioacetals with bromine undergo replacement of one alkylthio group by bromine. These unstable bromides react, as by fusion with 2,4-bis(trimethylsilyloxy)pyrimidine, to give acylated 1-(pyrimidin-1-yl) derivatives that upon saponification afford acyclic sugar nucleoside analogues, some as separable mixtures of 1-epimers. Systemic stereochemical variants have been conducted. Pmr conformational studies show that the sugar chain is extended in certain examples, whereas others favor folded ("sickle") conformations, in line with a general rationale developed for acyclic-sugar derivatives. Condensation of the bromides with purines gives 9-substituted acyclic-sugar nucleoside analogues; synthesized systematically for various series, these include the D-pentoses in combination with 6-mercaptopurine. In vitro and in vivo biological activities vary according to stereochemistry of the sugar. The position of substitution of the sugar chain, the chirality at C-1', and the tautomeric form of the heterocycle, were established by x-ray crystallography of the product from D-arabinose and 6-mercaptopurine. The x-ray data permit correlation of C-1 chirality throughout the series and pmr data indicate the favored conformations.
D001089:Arabinose / Q000031:analogs & derivatives; D001681:Biological Assay; D005690:Galactose / Q000031:analogs & derivatives; D005947:Glucose / Q000031:analogs & derivatives; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D008961:Models, Structural; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis*; D009905:Optical Rotatory Dispersion; D010429:Pentoses; D012266:Ribose / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D014994:Xylose / Q000031:analogs & derivatives
D009705:Nucleosides; D010429:Pentoses; D012266:Ribose; D014994:Xylose; D001089:Arabinose; D005947:Glucose; D005690:Galactose