Facile synthesis of orthogonally protected amino acid building blocks for combinatorial N-backbone cyclic peptide chemistry

The Journal of Peptide Research : Official Journal of the American Peptide Society
G GellermanM Kramer

Abstract

Protected Nalpha-(aminoallyloxycarbonyl) and Nalpha-(carboxyallyl) derivatives of all natural amino acids (except proline), and their chiral inverters, were synthesized using facile and efficient methods and were then used in the synthesis of Nalpha-backbone cyclic peptides. Synthetic pathways for the preparation of the amino acid building units included alkylation, reductive amination and Michael addition using alkylhalides, aldehydes and alpha,beta-unsaturated carbonyl compounds, and the corresponding amino acids. The resulting amino acid prounits were then subjected to Fmoc protection affording optically pure amino acid building units. The appropriate synthetic pathway for each amino acid was chosen according to the nature of the side-chain, resulting in fully orthogonal trifunctional building units for the solid-phase peptide synthesis of small cyclic analogs of peptide loops (SCAPELs). Nalpha-amino groups of building units were protected by Fmoc, functional side-chains were protected by t-Bu/Boc/Trt and N-alkylamino or N-alkylcarboxyl were protected by Alloc or Allyl, respectively. This facile method allows easy production of a large variety of amino acid building units in a short time, and is successfully employed in comb...Continue Reading

References

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Citations

Jul 1, 2010·Expert Opinion on Drug Discovery·Oded OvadiaHorst Kessler
Sep 15, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Genady KostenichArie Orenstein
Jun 23, 2015·Biopolymers·Ana I Fernández-LlamazaresFernando Albericio
Sep 4, 2003·Journal of Peptide Science : an Official Publication of the European Peptide Society·John S Davies
May 26, 2017·Biomedicines·Yosi GiladGary Gellerman
Dec 8, 2020·Frontiers in Chemistry·Alaa TalhamiChaim Gilon
Feb 2, 2011·Journal of Medicinal Chemistry·Marc VendrellMiriam Royo

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