title: Oxidative substitution of boranephosphonate diesters as a route to post-synthetically modified DNA.
abstract: The introduction of modifications into oligonucleotides is important for a large number of applications in the nucleic acids field. However, the method of solid-phase DNA synthesis presents significant challenges for incorporating many useful modifications that are unstable to the conditions for preparing synthetic DNA. Here we report that boranephosphonate diesters undergo facile nucleophilic substitution in a stereospecific manner upon activation by iodine. We have subsequently used this reactivity to post-synthetically introduce modifications including azides and fluorophores into DNA by first synthesizing boranephosphonate-linked 2'-deoxyoligonucleotides and then treating these oligomers with iodine and various nucleophiles. In addition, we show that this reaction is an attractive method for preparing stereodefined phosphorus-modified oligonucleotides. We have also examined the mechanism of this reaction and show that it proceeds via an iodophosphate intermediate. Beyond nucleic acids synthesis, due to the ubiquity of phosphate derivatives in natural compounds and therapeutics, this stereospecific reaction has many potential applications in organophosphorus chemistry.
authors: Department of Chemistry and Biochemistry, University of Colorado , Boulder, Colorado 80303, United States.
authors: Sibasish
authors: S
authors: Paul
authors: Subhadeep
authors: S
authors: Roy
authors: Luca
authors: L
authors: Monfregola
authors: Shiying
authors: S
authors: Shang
authors: Richard
authors: R
authors: Shoemaker
authors: Marvin H
authors: MH
authors: Caruthers
mesh_terms: D000577:Amides / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D001896:Boron Compounds / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D019281:Dimerization; D004952:Esters / Q000737:chemistry; D005021:Ethylamines / Q000737:chemistry; D007455:Iodine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*; D010084:Oxidation-Reduction; D010756:Phosphoric Acids / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D001386:Azides; D001896:Boron Compounds; D004952:Esters; D005021:Ethylamines; D009841:Oligonucleotides; D063065:Organophosphonates; D010756:Phosphoric Acids; C027070:N,N-diisopropylethylamine; D004247:DNA; D007455:Iodine; C011067:phosphoramidic acid