Oral Presentation 6th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2017

Green strategies for solid-phase peptide synthesis (GSPPS) (#10)

Yahya E. Jad 1 , Ashish Kumar 1 2 , Ayman El-Faham 3 4 , Jonathan M. Collins 5 , Fernando Albericio 1 2 3 6 7 , Beatriz G. de la Torre 1 8
  1. School of Health Sciences, University of KwaZulu-Natal, Durban, KWAZULU-NATAL, South Africa
  2. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
  3. Department of Chemistry-College of Science , King Saud University, Riyadh, Saudi Arabia
  4. Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
  5. CEM Corporation, Matthews, North Carolina 28104, United States
  6. Department of Organic chemistry, University of Barcelona, Barcelona, Spain
  7. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain
  8. School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa

The commonly employed solvents in peptide synthesis, DMF (the mostly used), NMP and DCM, are hazardous chemicals per several selection guides for greener chemistry.1 Moreover, solvents are the major component in all reaction mixtures. Thus, the search of greener alternatives is needed.

Herein, we are presenting studies about substituting DMF by greener solvents. Initially, 2-MeTHF and CPME were evaluated for peptide coupling reactions and 2-MeTHF showed promising results. Then, we applied EtOAc and IPA along with 2-MeTHF for full green SPPS (GSPPS) with the objective of totally avoiding DMF from the synthesis and we concluded that the use of 2-MeTHF for coupling and Fmoc removal steps with EtOAc washing steps is the best protocol in combination with ChemMatrix resin and DIC/OxymaPure. However, we found that Fmoc removal is problematic during SPPS of aggregated peptides which required performing the Fmoc removal at 40 °C. Therefore, another independent study was achieved for evaluation of green solvents for the Fmoc removal steps.2

A further step has been the implementation of the use of microwave heating. In this regard, the use of other solvents suitable for microwave technology have been investigated. γ-Valerolactone, which has a boiling point of 207 °C and is very safe regarding flammability and explosion, has shown to render excellent results using polystyrene resins. Consumed energy via microwave heating is more benefiting than the conventional heating because the energy goes directly to the liquid rather than vessel which can save some energy. Furthermore, the save of person-power and the high purity of the final products make microwave an asset in the green philosophy.

Overall conclusions of our studies are that there are green alternatives for the hazardous solvents and in several cases with even superior results.

  1. 1. D. Prat, A. Wells, J. Hayler, H. Sneddon, C. R. McElroy, S. Abou-Shehada, P. J. Dunn, Green Chem., 2016, 18, 288–296.
  2. 2. Y. E. Jad, T. Govender, H. G. Kruger, A. El-Faham, B. G. de la Torre, F. Albericio, Org. Process Res. Dev. 2017, 21, 365−369