Fluorenylmethyloxycarbonyl protecting group

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Fmoc1.png

The fluorenylmethyloxycarbonyl protecting group (Fmoc) is a base-labile protecting group used in organic synthesis.

Reactions[edit]

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]

Scheme showing addition of an Fmoc group to an amino acid

The other common method for introducing the Fmoc group is through 9-fluorenylmethylsuccinimidyl carbonate (Fmoc-OSu), which may itself be obtained by the reaction of Fmoc-Cl with the dicyclohexylammonium salt of N-hydroxysuccinimide.[2]

It may be cleaved by bases, typically a solution of piperidine:

Mechanism of the deprotection of the Fmoc group with piperidine.

Fmoc protection has found significant use in solid phase peptide synthesis because its removal with piperidine solution does not disturb the acid labile linker between the peptide and the resin.[3]

Because the fluorenyl group is highly fluorescent, certain UV-inactive compounds may be reacted to give the Fmoc derivatives, suitable for analysis by reversed phase HPLC. Analytical uses of Fmoc-Cl that do not use chromatography may be limited by the requirement that excess Fmoc-Cl be removed before an analysis of fluorescence.

Common amine protection methods[edit]

Common amine deprotection methods[edit]

References[edit]

  1. ^ Yamada, Kazuhiko; Hashizume, Daisuke; Shimizu, Tadashi; Ohki, Shinobu; Yokoyama, Shigeyuki (2008). "A solid-state 17O NMR, X-ray, and quantum chemical study of N-α-Fmoc-protected amino acids". Journal of Molecular Structure. 888: 187–196. doi:10.1016/j.molstruc.2007.11.059.
  2. ^ Paquet, A. (1982). "Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates". Canadian Journal of Chemistry. 60 (8): 976–980. doi:10.1139/v82-146. Archived from the original on 2012-07-26.
  3. ^ J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002.
  4. ^ Carpino, Louis A.; Han, Grace Y. (1972). "9-Fluorenylmethoxycarbonyl amino-protecting group". The Journal of Organic Chemistry. 37 (22): 3404–3409. doi:10.1021/jo00795a005.
  5. ^ Wuts, P; Green, T (2006); "Greene's Protective Groups in Organic Synthesis"; DOI: 10.1002/9780470053485.
  6. ^ Farrera-Sinfreu, Josep; Royo, Miriam; Albericio, Fernando (2002-10-21). "Undesired removal of the Fmoc group by the free ε-amino function of a lysine residue". Tetrahedron Letters. 43 (43): 7813–7815. doi:10.1016/S0040-4039(02)01605-2.