biostudies-literatureFrei SSwiss National Science Foundation3088-3097https://www.ebi.ac.uk/biostudies/studies/S-EPMC6317435biostudies-literatureUnknown14Here we report on the synthesis, biophysical properties and molecular modeling of oligonucleotides containing unsaturated 6'-fluoro[4.3.0]bicyclo nucleotides (6'F-bc^4,3-DNA). Two 6'F-bc^4,3 phosphoramidite building blocks (T and C) were synthesized starting from a previously described [3.3.0]bicyclic sugar. The conversion of this sugar to a <i>gem</i>-difluorinated tricyclic intermediate via difluorocarbene addition followed either by a NIS-mediated or Vorbrüggen nucleosidation yielded in both cases the β-tricyclic nucleoside as major anomer. Subsequent desilylation and cyclopropane ring opening of these tricyclic intermediates afforded the unsaturated 6'F-bc^4,3 nucleosides. The successful incorporation of the corresponding phosphoramidite building blocks inBeilstein journal of organic chemistry6'-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations.PMC6317435200020165778Leumann CJIstrate AFrei Sfalse6'-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations.Here we report on the synthesis, biophysical properties and molecular modeling of oligonucleotides containing unsaturated 6'-fluoro[4.3.0]bicyclo nucleotides (6'F-bc^4,3-DNA). Two 6'F-bc^4,3 phosphoramidite building blocks (T and C) were synthesized starting from a previously described [3.3.0]bicyclic sugar. The conversion of this sugar to a <i>gem</i>-difluorinated tricyclic intermediate via difluorocarbene addition followed either by a NIS-mediated or Vorbrüggen nucleosidation yielded in both cases the β-tricyclic nucleoside as major anomer. Subsequent desilylation and cyclopropane ring opening of these tricyclic intermediates afforded the unsaturated 6'F-bc^4,3 nucleosides. The successful incorporation of the corresponding phosphoramidite building blocks in2018-01-01T00:00:00Z20182026-05-07T02:51:30.815Z2019-03-26T22:36:52ZS-EPMC63174353064358610.3762/bjoc.14.288