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

Coupling reagents: Oxyma overcoming benzotriazoles (#45)

Yahya E. Jad 1 , Ashish Kumar 1 2 , Gerando A. Acosta 3 4 , Beatriz G. de la Torre 5 , Ayman El-Faham 6 7 , Fernando Albericio 2 3 4 6
  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 Organic chemistry, University of Barcelona, Barcelona, Spain
  4. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona, Spain
  5. School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa
  6. Department of Chemistry-College of Science , King Saud University, Riyadh, Saudi Arabia
  7. Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt

Just a few years ago coupling reagents were totally dominated by the hydroxybenzotriazole family, such as HOBt, Cl-HOBt, and HOAt with carbodiimides and HBTU, HCTU, and HATU as stand-alone reagents. The identification of the potential explosively of benzotriazole derivatives, turned the attention to develop new benzotriazole-free reagents. Later, our group proposed OxymaPure and it showed superior performance to HOBt and even in some cases superior to HOAt. Furthermore, we developed the morpholinium based uronium salt which in conjunction with OxymaPure render COMU.1 Herein, the last developments of the Oxyma family will be discussed.

Thus, Oxyma-B which takes advantage of a special orientation of the carbonyl moiety which can play an assisted basic catalyst role enhancing the nucleophilicity of the amino function during the coupling, makes Oxyma-B a superior additive to minimize racemization.

Potassium salts of OxymaPure and Oxyma-B helps to avoid the leaking of the growing peptide from the CTC-resin and their combination with EDC.HCl, the greenest carbodiimides, showed a superior performance than DIC. New solvents have been investigated that allows COMU to be kept in solution without significant destruction. COMU can be formed in situ from OxymaPure and DCMH or other stand-alone reagents, facilitating its use in automatic synthesizers. Fmoc-Oxyma are excellent reagents for a safe introduction of the Fmoc group.

As conclusion, it is possible to say that the Oxyma family is the reagent of choice for driven the formation of the peptide bond.

  1. Y. E. Jad, S. N. Khattab, B. G. de la Torre, T. Govender, H. G. Kruger, A. El-Faham, F. Albericio, Org. Biomol. Chem., 2014, 12, 8379–8385.