Synlett 2014; 25(13): 1843-1846
DOI: 10.1055/s-0034-1378330
letter
© Georg Thieme Verlag Stuttgart · New York

A One-Pot Saponification–Coupling Sequence Suitable for C-Terminus Peptide Elongation Using Lithium Carboxylates

Rabah Azzouz
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 rue Tesnière, 76821 Mont Saint Aignan Cedex, France   Fax: +33(235)522962   Email: laurent.bischoff@univ-rouen.fr
,
Sylvain Petit
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 rue Tesnière, 76821 Mont Saint Aignan Cedex, France   Fax: +33(235)522962   Email: laurent.bischoff@univ-rouen.fr
,
Jean-Baptiste Rouchet
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 rue Tesnière, 76821 Mont Saint Aignan Cedex, France   Fax: +33(235)522962   Email: laurent.bischoff@univ-rouen.fr
,
Laurent Bischoff*
Normandie Univ, COBRA, UMR 6014 et FR 3038, Univ Rouen, INSA Rouen, CNRS, IRCOF, 1 rue Tesnière, 76821 Mont Saint Aignan Cedex, France   Fax: +33(235)522962   Email: laurent.bischoff@univ-rouen.fr
› Author Affiliations
Further Information

Publication History

Received: 08 April 2014

Accepted after revision: 23 May 2014

Publication Date:
08 July 2014 (online)


Abstract

An efficient procedure has been developed for the saponification of common peptide esters, followed by straightforward coupling of the lithium carboxylate. Adding some water to the reaction medium gave faster saponification and did not interfere with the coupling reagent. As peptide chemistry constitutes a major application of the amidation reaction, amino acid substrates were chosen for this study, monitoring both yields and epimerization of the peptides obtained.

Supporting Information

 
  • References and Notes

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  • 11 General Procedure for the Formation of Carboxylates and Subsequent Coupling Reaction: To a solution of Cbz-Ala-Phe-OMe (0.3 g, 0.81 mmol) in dioxane (2 mL) at r.t. were added LiOH (25 mg, 1 mmol) and H2O (0.35 mL, 19.44 mmol, 24 molar equiv). Stirring at r.t. and monitoring by HPLC showed complete saponification and a clear, homogeneous solution generally after 3 h. Amino acid H-AA-OMe, HCl (0.9 mmol) and HATU (0.463 g, 1.22 mmol) were added and the mixture was stirred at r.t. until completion, generally 4 h. The diastereomeric purity was measured at this stage, before isolation and purification. After concentration in vacuo, the residue was purified by silica gel chromatography with a mixture of CH2Cl2–EtOAc as eluent to afford the pure tripeptide as a white solid