ABSTRACT
Short oligonucleoside boranophosphates containing all four nucleosides were synthesized on solid support using base-unprotected nucleoside H-phosphonate monomers. This strategy avoided irreversible base modifications during the boronation procedure. Structures of the boranophosphate oligomers were confirmed by 1H, 31P, 10B NMR and MS analysis as well as by enzymatic hydrolysis.
Subject(s)
Boron Compounds/chemical synthesis , Oligonucleotides/chemical synthesis , Organophosphonates/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
A new method for synthesis of N-alkylated nucleosides was developed. Exceptionally mild and selective conversion of N-acyl to the corresponding N-alkyl nucleosides was achieved by reduction with borane-amine complexes. The borane-amine complexes were also used as efficient scavengers of a 4,4'-dimethoxytrityl (DMT) cation. Neutralization of the cation eliminated the boranophosphate group degradation during acidic DMT deprotection and allowed milder acidic conditions for the deprotection.
Subject(s)
Amines/chemistry , Boranes/chemistry , Nucleosides/chemical synthesis , Alkylation , Reducing Agents/chemistry , Trityl Compounds/chemistryABSTRACT
Borane-amine complexes provide an unusually fast and selective reduction of a deoxynucleoside N-acyl group to a corresponding N-alkyl group. Three different nucleosides (dG, dA, and dC) each having one of three N-protecting groups (benzoyl, isobutyryl, or acetyl) were used to prepare N-alkylated nucleosides in good yields under mild conditions. Deoxyribose O-acyl protecting groups remain intact at the conditions of N-acyl group reduction.
Subject(s)
Amides/chemistry , Boranes/chemistry , Nucleosides/chemistry , Amines/chemistry , Chromatography, High Pressure Liquid , Magnetic Resonance Spectroscopy , Oxidation-ReductionABSTRACT
Nucleoside boranophosphates are distinctive in that one of the non-bridging oxygens in the phosphate diester 1 is replaced by a borane moiety (BH3). Although they retain the same net charge, BH3(-)-ODN have unique chemical and biochemical characteristics relative to other analogs. The change in polarity, lipophilicity, nuclease resistance, and the activation of RNase H cleavage of RNA in RNA: boranophosphate hybrids make boranophosphates very attractive for applications in enzymology and molecular biology and as potential antisense agents.
