Synthesis and Properties of 4′-ThioLNA/BNA
Rion Maeda, Noriko Saito–Tarashima, Hideaki Wakamatsu, Yoshihiro Natori, Noriaki Minakawa, Yuichi Yoshimura
Abstract
To develop a new nucleoside analogue applicable to oligonucleotide therapeutics, we designed a 4′-thio analogue of an LNA/BNA monomer. Synthesis of 4′-hydroxymethyl-4′-thioribonucleoside was achieved by a tandem ring-contraction-aldol reaction of a 5-thiopyranose derivative and the subsequent Pummerer-type thioglycosylation reaction of the corresponding sulfoxide. Treatment of 4′-hydroxymethyl-4′-thiopyrimidine nucleosides with diphenyl carbonate in the presence of catalytic NaHCO3 gave the desired 4′-thioLNA/BNA monomers, which were introduced into oligonucleotides.
Topics & Concepts
ChemistryMonomerThio-OligonucleotideHydroxymethylAldol reactionCombinatorial chemistryNucleosideSulfoxideDerivative (finance)StereochemistryOrganic chemistryCatalysisPolymerDNABiochemistryFinancial economicsEconomicsAdvanced biosensing and bioanalysis techniquesDNA and Nucleic Acid ChemistryRNA Interference and Gene Delivery