The use of crown ethers in peptide chemistry IV. Solid phase synthesis of peptides using peptide fragments Nα protected with 18-crown-6

Paolo Botti, Haydn L. Ball, Emanuele Rizzi, Pierluigi Lucietto, Massimo Pinori, Paolo Mascagni

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The conditions under which peptide synthesis by the fragment condensation approach in the solid phase can be carried out using crown ethers as non-covalent protecting groups for the Nα amino group of peptides were determined. The dipeptide Gly-Gly was complexed with 18-crown-6 to establish the feasibilty of this new protection scheme and to optimise the reaction conditions. Nearly quantitative incorporation of the complex onto resin-bound amino acids possessing either proline or an Nα-alkylated amino acids was achieved using DCM as the activation and coupling reactions solvent. The use of DMF as the solvent and resin-bound primary amino acids were found detrimental to the reaction yields due to the removal of the crown ether protection. Extending the length of the peptide fragment to model pentapeptide complexes bearing no reactive functionalities on the side-chain gave essentially quantitative incorporation yields in the coupling reactions to both resin-bound amino acids and short peptides. The non-covalent nature of the protection afforded by the crown molecule allowed its mild removal from resin-bound complexes by rapid treatments with 1% DIEA solutions. Thus the continuation of chain assembly was possible. The results obtained served as the basis for extending the concept of non-covalent protection to the side chains of Lys and Arg containing peptides.

Original languageEnglish (US)
Pages (from-to)5447-5458
Number of pages12
JournalTetrahedron
Volume51
Issue number18
DOIs
StatePublished - May 1 1995

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ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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