Extended Data Fig. 7: Friedländer macrocyclization and DNA stability with high equivalents of Yb(OTf)3 in aqueous acetonitrile.
From: Chemical and ribosomal synthesis of atropisomeric and macrocyclic peptides with embedded quinolines
Scheme (a) and Total Ion Chromatograms (b-e) of Friedländer macrocyclization of LP2 (1 mM or 10 µM) with Yb(OTf)3 (1 mM, 10 mM, 100 mM or 200 mM) in H2O/MeCN (1:1 v/v). TIC conversions are averages of three independent replicates. Data is representative. Conversion of Friedländer macrocyclization is dramatically reduced in highly aqueous environments, but reactivity can be rescued with high equivalents of Yb(OTf)3. f, Stability of an oligonucleotide DNA:RNA duplex was assessed under aqueous acetonitrile Friedländer macrocyclization conditions in the presence of 200 mM Yb(OTf)3. Absorbance chromatogram (g) and extracted ion chromatogram (h) showing that RNA is degraded while DNA remains stable under reaction conditions. dFx was used as an internal standard to control for ionization efficiency across samples. Samples were run in triplicate, and representative traces are shown. i, Stability of RNA and DNA when exposed to reaction conditions. We suspect that the higher recovery of the DNA post-reaction is a result of improved DNA precipitation and column retention because of the Yb(OTf)3 salt compared to the unreacted sample. Error bars represent standard deviation (SD). j, Mass spectra of DNA before and after reaction are identical.
