title: Practical synthesis of 4'-thioribonucleosides starting from D-ribose.
abstract: A practical synthesis of 4'-thioribonucleosides, i.e., 4'-thiouridine, -cytidine, -adenosine, and -guanosine, which are versatile units for nucleic acids-based therapeutics, is described. Large-scale synthesis of 4-thiosugar starting from D-ribose was achieved (33%) in eight steps and with only three chromatographic purifications. After the appropriate chemical conversion of the 4-thiosugar, the resulting sulfoxide was subjected to the Pummerer reaction in the presence of silylated nucleobases. In reactions with silylated pyrimidine bases, the desired 4'-thioribonucleoside derivatives were obtained in good yield and β-selectively. On the other hand, N-7 isomers were obtained mainly in the Pummerer reaction with purine bases under the same conditions. However, the desired N-9 isomers were obtained in moderate yields when the reaction mixtures were subsequently heated under reflux. As a result, effective synthesis of 4'-thioribonucleosides was accomplished.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Minakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D012266:Ribose / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D012263:Ribonucleosides; D013438:Sulfhydryl Compounds; D012266:Ribose
keywords: 4-thiosugar; 4′-thioribonucleoside; D-ribose; Pummerer reaction; sulfoxide