Fmoc Deprotection Reagents

Fmoc Deprotection Reagents

Published on 14/09/2017

The Fmoc group is the most frequently used protecting group in peptide chemistry. The most common deprotection conditions involve a solution of 20% piperidine in DMF.

However, in case of difficult or sensitive sequences, there are alternative deprotection reagents that can be employed, such as the non-nucleophilic base DBU in DMF. Another useful alternative to piperidine is 4-methylpiperidine, which has been shown to deprotect the Fmoc group as efficiently as piperidine (Hachmann and Lebl, J. Comb. Chem. 2006).

An additional benefit of both DBU and 4-methylpiperidine is that in contrast to piperidine, these compounds are no controlled substances and do not require an end-user declaration. While piperidine requires a lot of paperwork and is subject to various export limitations, this is not the case for DBU and 4-methylpiperidine.

In our webshop you can find all these tried and tested reagents for Fmoc removal. The latest addition to this range is a premixed solution of 20% piperidine in DMF that can be conveniently used straight out of the bottle.

Removal of the relatively acidic proton on C9 of the fluorenyl moiety by piperidine.

→ Be prepared for the step following Fmoc deprotection: check out our large selection of Coupling Reagents.


  • Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences; I. Coin, M. Beyermann and M. Bienert; Nat. Protocols 2007; 2: 3247-3256.
  • Methods and protocols of modern solid phase peptide synthesis; M. Amblard, J.-A. Fehrentz, J. Martinez and G. Subra; Molecular Biotechnology 2006; 33: 239-254. doi:10.1385/mb:33:3:239
  • Alternative to Piperidine in Fmoc Solid-Phase Synthesis; J. Hachmann and M. Lebl; Journal of Combinatorial Chemistry 2006; 8: 149-149. doi:10.1021/cc050123l
  • The aspartimide problem in Fmoc-based SPPS. Part I; M. Mergler, F. Dick, B. Sax, P. Weiler and T. Vorherr; Journal of Peptide Science 2003; 9: 36-46. doi:10.1002/psc.430
  • An accurate method for the quantitation of Fmoc-derivatized solid phase supports; M. Gude, J. Ryf and P. D. White; Letters in Peptide Science 2002; 9: 203-206. doi:10.1007/bf02538384
  • Improved preparation of amyloid-β peptides using DBU as Nα-Fmoc deprotection reagent; A. K. Tickler, C. J. Barrow and J. D. Wade; Journal of Peptide Science 2001; 7: 488-494. doi:10.1002/psc.342
  • Optimized preparation of deca(L-alanyl)-L-valinamide by 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis on polyethylene glycol-polystyrene (PEG-PS) graft supports, with 1,8-diazobicyclo [5.4.0]-undec-7-ene (DBU) deprotection; S. A. Kates, N. A. Solé, M. Beyermann, G. Barany and F. Albericio; Peptide research 1996; 9: 106-113.
  • 3-(1-Piperidinyl)alanine formation during the preparation of C-terminal cysteine peptides with the Fmoc/t-Bu strategy; J. Lukszo, D. Patterson, F. Albericio and S. A. Kates; Letters in Peptide Science 1996; 3: 157-166. doi:10.1007/bf00132978
  • Methods for Removing the Fmoc Group; G. B. Fields; Peptide Synthesis Protocols M. W. Pennington and B. M. Dunn 1995: 17-27. doi:10.1385/0-89603-273-6:17
  • Susceptibility of glycans to β-elimination in Fmoc-based O-glycopeptide synthesis; M. Meldal, T. I. M. Bielfeldt, S. Peters, K. J. Jensen, H. Paulsen and K. Bock; International journal of peptide and protein research 1994; 43: 529-536. doi:10.1111/j.1399-3011.1994.tb00554.x
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