Abstract
Novel deprotection method of the Fmoc (9-flurorenylmethoxycarbonyl) protective group under Pd/C-catalyzed hydrogenation conditions at room temperature was developed. The addition of CH3CN accelerated the deprotection of the Fmoc group, and also the application of H2 pressure (3 atm) shows notable rate enhancement.
Similar content being viewed by others
References
Atherton E, Bury C, Sheppard RC, Williams BJ (1979) Stability of fluorenylmethoxycarbonylamino groups in peptide synthesis. Cleavage by hydrogenolysis and by dipolar aprotic solvents. Tetrahedron Lett 20:3041–3042
Atherton E, Logan CJ, Sheppard RC (1981) Peptide synthesis. Part 2. Procedures for solid-phase synthesis using Nα-fluorenylmethoxycarbonyl amino acids on polyamide supports. Synthesis of substance P and of acyl carrier protein 65–74 decapeptide. J Chem Soc Perkin Trans 1:538–546
Carpino LA, Han GY (1970) 9-Fluorenylmethoxycarbonyl function, a new base-sensitive amino-protecting group. J Am Chem Soc 92:5748–5749
Carpino LA, Han GY (1972) 9-Fluorenylmethoxycarbonyl amino-protecting group. J Org Chem 37:3404–3409
Carpino LA, Williams JR, Lopusinski A (1978) Polymeric de-blocking agents for the fluoren-9-ylmethoxycarbonyl (FMOC) amino-protecting group. J Chem Soc Chem Commun 450–451
Carpino LA, Mansour EME, Knapczyk J (1983) Piperazino-functionalized silica gel as a deblocking-scavenging agent for the 9-fluorenylmethyloxycarbonyl amino-protecting group. J Org Chem 48:666–669
Carpino LA, Cohen BJ, Stephens KE Jr, Sadat-Aalaee SY, Tien J-H, Langridge DC (1986) (Fluoren-9-ylmethoxy) carbonyl (Fmoc) amino acid chlorides. Synthesis, characterization, and application to the rapid synthesis of short peptide segments. J Org Chem 51:3732–3734
Dzubeck V, Schneider JP (2000) One-pot conversion of benzyl carbamates into fluorenylmethyl carbamates. Tetrahedron Lett 41:9953–9956
Ho PT, Ngu K (1994) A practical synthesis of optically pure and fully protected l-γ-carboxyglutamic acid derivatives and its application in peptide synthesis. Pept Res 7:249–254
Kelly RC, Gebhard I, Wicnienski N (1986) Synthesis of (R)- and (S)-(glu) thz and the corresponding bisthiazole dipeptide of dolastatin 3. J Org Chem 51:4590–4594
Kocieński PJ (2005) Protecting groups, 3rd edn. Georg Thieme Verlag, Germany
Leggio A, Liguori A, Napoli A, Siciliano C, Sindona G (2000) New strategies for an efficient removal of the 9-fluorenylmethoxycarbonyl (Fmoc) protecting group in the peptide synthesis. Eur J Org Chem 573–575
Martinez J, Tolle JC, Bodanszky M (1979) Side reactions in peptide synthesis. 12. Hydrogenolysis of the 9-fluorenylmethyloxycarbonyl group. J Org Chem 44:3596–3598
Nicolaou KC, Groneberg RD, Miyazaki T, Stylianides NA, Schulze TJ, Stahl W (1990) Total synthesis of the oligosaccharide fragment of calicheamicin.gamma.II. J Am Chem Soc 112:8193–8195
Nishimura S (2001) Handbook of heterogeneous catalytic hydrogenation for organic synthesis. Wiley-Interscience, New York
Pearson AJ, Roush WR (1999) Handbook of reagents for organic synthesis, activating agents and protecting groups. Wiley, Chichester
Rylander PN (1985) Hydrogenation methods. Academic Press, New York
Sajiki H, Ikawa T, Hirota K (2004) Reductive and catalytic monoalkylation of primary amines using nitriles as an alkylating reagent. Org Lett 6:4977–4980
Schmidt U, Mundinger K, Mangold R, Lieberknecht A (1990) Amino acids and peptides. 76. Lavendomycin: total synthesis and assignment of configuration. J Chem Soc Chem Commun 1216–1219
Theodorou V, Ragoussis V, Strongilos A, Zelepos E, Eleftheriou A, Dimitriou M (2005) A convenient method for the preparation of primary amines using tritylamine. Tetrahedron Lett 46:1357–1360
Ueki M, Amemiya M (1987) Removal of the 9-fluorenylmethyloxycarbonyl (Fmoc) group with tetrabutylammonium fluoride. Tetrahedron Lett 28:6617–6620
Ueki M, Nishigaki N, Aoki H, Tsurusaki T, Katoh T (1993) One-pot deprotection and coupling of peptides by the Fmoc strategy. Chem Lett 22:721–724
Wuts PGM, Greene TW (2007) Greene’s protective groups in organic synthesis, 4rd edn. Wiley, New York
Acknowledgment
We thank N. E. Chemcat Corporation for a gift of 10% Pd/C.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maegawa, T., Fujiwara, Y., Ikawa, T. et al. Novel deprotection method of Fmoc group under neutral hydrogenation conditions. Amino Acids 36, 493–499 (2009). https://doi.org/10.1007/s00726-008-0109-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-008-0109-7