Elsevier

Tetrahedron Letters

Volume 43, Issue 43, 21 October 2002, Pages 7813-7815
Tetrahedron Letters

Undesired removal of the Fmoc group by the free ε-amino function of a lysine residue

https://doi.org/10.1016/S0040-4039(02)01605-2Get rights and content

Abstract

In solid-phase peptide synthesis, a side-reaction consisting of the premature and undesired removal of the Fmoc group has been detected. This can be caused by a primary amine of sufficient basicity, such as the ε-amino of the Lys, present in the peptide resin. This side-reaction, which is not promoted by either the β-amino side-chain of the Dapa residue or the α-amino group, can be prevented by a coupling/neutralization protocol in the case of Mtt protection or by a tandem deprotection–coupling reaction in the case of Alloc protection. The same kind of side-reaction has been detected when amino side-chain functions of Orn or Daba are free in the peptide resin.

In solid-phase peptide synthesis, a side-reaction consisting of the premature and undesired removal of the Fmoc group has been detected. This can be caused by a primary amine of sufficient basicity, such as the ε-amino of the Lys, present in the peptide resin. This side-reaction can be prevented by a coupling/neutralization protocol in the case of Mtt protection or by a tandem deprotection–coupling reaction for the case of the Alloc protection.

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Acknowledgements

We thank Dr. Victor Segarra from Almirall-Prodesfarma for the pKa calculations. M.R. is a ‘Ramon y Cajal’ fellow (MCyT, Spain). This work was partially supported by CICYT (BQU2000-0235), Generalitat de Catalunya (Grup Consolidat, and Centre de Referència en Biotecnologia).

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