A convenient route to N-[2-(Fmoc)aminoethyl]glycine esters and PNA oligomerization using a Bis-N-Boc nucleobase protecting group strategy

J Org Chem. 2008 May 16;73(10):3807-16. doi: 10.1021/jo800195j. Epub 2008 Apr 16.

Abstract

A simple and practical synthesis of the benzyl, allyl, and 4-nitrobenzyl esters of N-[2-(Fmoc)aminoethyl]glycine is described starting from the known N-(2-aminoethyl)glycine. These esters are stored as stable hydrochloride salts and were used in the synthesis of peptide nucleic acid monomers possessing bis-N-Boc-protected nucleobase moieties on the exocyclic amino groups of ethyl cytosin-1-ylacetate, ethyl adenin-9-ylacetate and ethyl (O(6)-benzylguanin-9-yl)acetate. Upon ester hydrolysis, the corresponding nucleobase acetic acids were coupled to N-[2-(Fmoc)aminoethyl]glycine benzyl ester or to N-[2-(Fmoc)aminoethyl]glycine allyl ester in order to retain the O(6) benzyl ether protecting group of guanine. The Fmoc/bis-N-Boc-protected monomers were successfully used in the Fmoc-mediated solid-phase peptide synthesis of mixed sequence 10-mer PNA oligomers and are shown to be a viable alternative to the currently most widely used Fmoc/Bhoc-protected peptide nucleic acid monomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esters / chemical synthesis*
  • Esters / chemistry
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Molecular Structure
  • Peptide Nucleic Acids / chemistry*
  • Stereoisomerism

Substances

  • Esters
  • Peptide Nucleic Acids
  • Glycine