Fluorenylmethyloxycarbonyl protecting group: Difference between revisions
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Hurtsville (talk | contribs) Added some additional details regarding the use of piperidine for deprotection in SPPS. |
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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|''N''-hydroxysuccinimide]].<ref>{{cite journal | author = Paquet, A. | title = Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates | journal = [[Canadian Journal of Chemistry]] | volume = 60 | pages = 976–980 | year = 1982 | doi = 10.1139/v82-146 | issue = 8 | doi-access = free}}</ref> |
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|''N''-hydroxysuccinimide]].<ref>{{cite journal | author = Paquet, A. | title = Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates | journal = [[Canadian Journal of Chemistry]] | volume = 60 | pages = 976–980 | year = 1982 | doi = 10.1139/v82-146 | issue = 8 | doi-access = free}}</ref> |
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The Fmoc group is rapidly removed by primary bases as well as some secondary bases. 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.<ref>{{Citation|last=Fields|first=Gregg B.|title=Methods for Removing the Fmoc Group|date=1995|url=https://doi.org/10.1385/0-89603-273-6:17|work=Peptide Synthesis Protocols|pages=17–27|editor-last=Pennington|editor-first=Michael W.|series=Methods in Molecular Biology|place=Totowa, NJ|publisher=Humana Press|language=en|doi=10.1385/0-89603-273-6:17|isbn=978-1-59259-522-8|access-date=2021-10-15|editor2-last=Dunn|editor2-first=Ben M.}}</ref> Fmoc protection has found significant use in [[solid phase peptide synthesis]] (SPPS), because its removal with piperidine solution does not disturb the acid labile linker between the peptide and the resin.<ref>J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002</ref> A typical SPPS Fmoc deprotection is performed with a 20% solution of piperidine in N,N-dimethylformamide.<ref name=":0" /> |
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It may be cleaved by bases, typically a solution of [[piperidine]]: |
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:[[File:Fmoc cleavage.gif|400px|Mechanism of the deprotection of the Fmoc group with piperidine]] |
:[[File:Fmoc cleavage.gif|400px|Mechanism of the deprotection of the Fmoc group with piperidine]] |
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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.<ref>J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002</ref> |
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Because the fluorenyl group is highly fluorescent, certain UV-inactive compounds may be reacted to give the Fmoc derivatives, suitable for analysis by [[High performance liquid chromatography#Reversed phase chromatography|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]]. |
Because the fluorenyl group is highly fluorescent, certain UV-inactive compounds may be reacted to give the Fmoc derivatives, suitable for analysis by [[High performance liquid chromatography#Reversed phase chromatography|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]]. |
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=== Common amine deprotection methods === |
=== Common amine deprotection methods === |
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* 20% piperidine in [[dimethylformamide]] (Fmoc group has an approximate half life of 6 seconds in this solution)<ref>Wuts, P; Green, T (2006); "Greene's Protective Groups in Organic Synthesis"; DOI: 10.1002/9780470053485.</ref> |
* 20% piperidine in [[dimethylformamide]] (Fmoc group has an approximate half life of 6 seconds in this solution)<ref name=":0">Wuts, P; Green, T (2006); "Greene's Protective Groups in Organic Synthesis"; DOI: 10.1002/9780470053485.</ref> |
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==References== |
==References== |
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Revision as of 02:24, 15 October 2021
The fluorenylmethoxycarbonyl protecting group (Fmoc) is a base-labile protecting group used in organic synthesis.
Reactions
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 9-fluorenylmethylsuccinimidyl carbonate (Fmoc-OSu), which may itself be obtained by the reaction of Fmoc-Cl with the dicyclohexylammonium salt of N-hydroxysuccinimide.[2]
The Fmoc group is rapidly removed by primary bases as well as some secondary bases. 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.[3] Fmoc protection has found significant use in solid phase peptide synthesis (SPPS), because its removal with piperidine solution does not disturb the acid labile linker between the peptide and the resin.[4] A typical SPPS Fmoc deprotection is performed with a 20% solution of piperidine in N,N-dimethylformamide.[5]
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
- Fluorenylmethyloxycarbonyl chloride or 9-fluorenylmethyloxycarbonyl azide (itself made by reacting Fmoc-Cl with sodium azide), sodium bicarbonate and aqueous dioxane[6]
Common amine deprotection methods
- 20% piperidine in dimethylformamide (Fmoc group has an approximate half life of 6 seconds in this solution)[5]
References
- ^ 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 (1–3): 187–196. doi:10.1016/j.molstruc.2007.11.059.
- ^ 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.
- ^ Fields, Gregg B. (1995), Pennington, Michael W.; Dunn, Ben M. (eds.), "Methods for Removing the Fmoc Group", Peptide Synthesis Protocols, Methods in Molecular Biology, Totowa, NJ: Humana Press, pp. 17–27, doi:10.1385/0-89603-273-6:17, ISBN 978-1-59259-522-8, retrieved 2021-10-15
- ^ J. Jones, Amino Acid and Peptide Synthesis, 2nd edn., Oxford University Press, 2002
- ^ a b Wuts, P; Green, T (2006); "Greene's Protective Groups in Organic Synthesis"; DOI: 10.1002/9780470053485.
- ^ 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.