α-Azido Acids in Solid-Phase Peptide Synthesis: Compatibility with Fmoc Chemistry and an Alternative Approach to the Solid Phase Synthesis of Daptomycin Analogs

J Org Chem. 2016 Mar 18;81(6):2624-8. doi: 10.1021/acs.joc.5b02882. Epub 2016 Mar 3.

Abstract

α-Azido acids have been used in solid phase peptide synthesis (SPPS) for almost 20 years. Here we report that peptides bearing an N-terminal α-azidoaspartate residue undergo elimination of an azide ion when treated with reagents that are commonly used for removing the Fmoc group during SPPS. We also report an alternative solid-phase route to the synthesis of an analog of daptomycin that uses a reduced number of α-azido amino acids and without elimination of an azide ion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry*
  • Daptomycin / chemical synthesis*
  • Daptomycin / chemistry
  • Indicators and Reagents / chemistry*
  • Peptides / chemical synthesis*
  • Peptides / chemistry
  • Solid-Phase Synthesis Techniques

Substances

  • Amino Acids
  • Indicators and Reagents
  • Peptides
  • Daptomycin