6'-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations.

ABSTRACT: 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 gem-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 in

SUBMITTER: Frei S 

PROVIDER: S-EPMC6317435 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature