Peptide isolation

Diethyl ether and TBME are the most widely used for precipitation after cleavage from the resin/global deprotection. As might be expected, several alternatives with better health and safety properties have been investigated. These include:

  • Cyclopentyl methyl ether (CPME)
  • 4-methyltetrahydropyran (MTHP)/n-heptane
  • 2-MeTHF

Al Musaimi, O.; Jad, Y. E.; Kumar, A.; Collins, J. M.; Basso, A.; de la Torre, B. G.; Albericio, F.  Investigating green ethers for the precipitation of peptides after global deprotection in solid-phase peptide synthesis. Curr. Opin. Green Sustain. Chem. 2018, 11, 99–103.

Pawlas, J.; Antonic, B.; Lundqvist, M.; Svensson, T.; Finnman, J.; Rasmussen, J. H. 2D green SPPS: green solvents for on-resin removal of acid sensitive protecting groups and lactamization. Green Chem. 2019, 21, 2594–2600.

Al Musaimi, O.; Jad, Y. E.; Kumar, A.; El-Faham, A.; Collins, J. M.; Basso, A.; de la Torre, B. G.; Albericio, F. Greening the Solid-Phase Peptide Synthesis Process. 2-MeTHF for the Incorporation of the First Amino Acid and Precipitation of Peptides after Global Deprotection. Org. Process Res. Dev. 2018, 22, 1809–1816.

E. Jad, Y. E.; Acosta, G. A.; Govender, T.; Kruger, H. G.; El-Faham, A.; de la Torre, B. G.; Albericio, F. Green Solid-Phase Peptide Synthesis 2. 2 Methyltetrahydrofuran and Ethyl Acetate for Solid-Phase Peptide Synthesis under Green Conditions. ACS Sustainable Chem. Eng. 2016, 4, 6809−6814.

© 2015 Green Chemistry Institute Pharmaceutical Roundtable. All rights reserved.