Poster Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

Fmoc group removal with NaOH in mixtures of water and green solvents during SPPS on biodegradable resin-ℇ-poly -Lys resin (#120)

Feng Lin 1 , Don Wellings 2 , M. Akhter Hossain 1 , John Wade 1
  1. Florey Neuroscience Institute, University of Melbourne, Melbourne, VIC 3010, Australia
  2. SpheriTech Ltd, Runcorn, Cheshire, UK,WA7 4QX

The Fmoc (Fluorenylmethyloxycarbonyl) group is the most important temporary protecting group of the α-amino group in Fmoc peptide chemistry. It can be removed with 20% piperidine in DMF (Dimethylformamide)[1,2] and under other basic conditions[3]. However piperidine is toxic[4] and DMF is harmful and had been proposed to the Annex XVII REACH restriction list by The European Commission [5] . In order to replace piperidine and DMF, we used NaOH as a Fmoc removal reagent in a mixture of water and other green solvents such as ethanol, MeOH and DMSO, the Fmoc group was removed successfully under mild conditions during SPPS the biodegradable resin-ℇ-poly -Lys solid support.

 

  1. Atherton, E, Fox, H., Harkiss, D., Logan, J., Sheppard, R, and Williams, B. J. (1978) A mild procedure for solid phase peptide synthesis: use of fluorenyl-methoxycarbonylamino-acids J. Chem. Soc, Chem Commun 537–539.
  2. Atherton, E., Fox, H, Harkiss, D, and Sheppard, R. C (1978) Application of polyamide resins to polypeptide synthesis: an improved synthesis of β-endorphin using fluorenylmethoxycarbonylamino-acids. J. Chem. Soc., Chem Commun 539,540.
  3. Michael W. Pennington and Ben M. Dunn (1995) Peptide Synthesis Protocols pp 17-27. Part of the Methods in Molecular Biology book series (edited by Gregg B. Fields), (MIMB, volume 35)
  4. European Chemicals Agency-Piperidine, https://echa.europa.eu/substance-information/-/substanceinfo/100.003.467.
  5. Chemical Watch, 06 October 2020, https://chemicalwatch.com/162874/eu-commission-proposes-reach-restriction-on-uses-of-dmf.