Fluorenylmethyloxycarbonyl protecting group
The fluorenylmethoxycarbonyl protecting group (Fmoc) is a base-labile protecting group used in organic synthesis.
Protection & Formation
Fmoc carbamate is frequently used as a protecting group for amines, where the Fmoc group can be introduced by reacting the amine with fluorenylmethyloxycarbonyl chloride (Fmoc-Cl), e.g.:[1]
The other common method for introducing the Fmoc group is through
Reacting with
Because the fluorenyl group is highly fluorescent, certain UV-inactive compounds may be reacted to give the Fmoc derivatives, suitable for analysis by
Cleavage & Deprotection
The Fmoc group is rapidly removed by base. Piperidine is usually preferred for Fmoc group removal as it forms a stable adduct with the dibenzofulvene byproduct, preventing it from reacting with the substrate.[4][5]
Roles in SPPS
The use of Fmoc as a temporary protecting group for amine at the
- C13H9−CH2−OC(O)NHR + (CH2)5NH → (CH2)5NH+2 + [C13H8−CH2−OC(O)NHR]−
- [C13H8−CH2−OC(O)NHR]− → C13H8=CH2 + −OC(O)NHR
- −OC(O)NHR + (CH2)5NH+2 → HOC(O)NHR + (CH2)5NH
- HOC(O)NHR → CO2 + RNH2
- C13H8=CH2 + (CH2)5NH → C13H9−CH2N(CH2)5
Common deprotection cocktails for Fmoc during SPPS:
- 20% piperidine in DMF (Fmoc group has an approximate half life of 6 seconds in this solution)[7]
- 5% piperazine, 1% DBU and 1% formic acid in DMF. This method avoids the use of strictly controlled piperidine.[8] No side product was observed for a peptide with 9 residues synthesized with this method.[9]
References
- .
- doi:10.1139/v82-146.
- .
- PMID 7894598, retrieved 2021-10-15
- PMID 9353717.
- ^ J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002
- ^ ISBN 9780470053485.
- ISSN 2046-2069.
- S2CID 247175352.
External links
Media related to Fmoc at Wikimedia Commons
