Synthesis of ( R)- and ( S)-Fmoc-Protected Diethylene Glycol Gamma PNA Monomers with High Optical Purity

J Org Chem. 2019 Feb 1;84(3):1276-1287. doi: 10.1021/acs.joc.8b02714. Epub 2019 Jan 22.


A robust synthetic route has been developed for preparing optically pure, Fmoc-protected diethylene glycol-containing ( R)- and ( S)-γPNA monomers. The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of epimerization in the O-alkylation and reductive amination steps. The optical purities of the final monomers were determined to be greater than 99.5% ee, as assessed by 19F-NMR and HPLC. The new synthetic methodology is well-suited for large-scale monomer production, with most synthetic steps providing excellent chemical yields without the need for chromatographic purification other than a simple workup and precipitation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromatography, High Pressure Liquid
  • Ethylene Glycols / chemical synthesis*
  • Macromolecular Substances / chemical synthesis*
  • Peptides / chemistry*


  • Ethylene Glycols
  • Macromolecular Substances
  • Peptides
  • diethylene glycol