2-Methf and CPME for Green Solid-Phase Peptide Synthesis

Supporting information

2-MeTHF and CPME for Green Solid-Phase Peptide Synthesis

Yahya E. Jad,1 Gerardo A. Acosta,2,3 Sherine N. Khattab,4 Beatriz G. de la Torre,1 Thavendran Govender,1 Hendrik G. Kruger,1 Ayman El-Faham*4,5 and Fernando Albericio*1,2,3,5,6,7

1Catalysis and Peptide Research Unit, School of Health Sciences, University ofKwaZulu-Natal, Durban 4001, South Africa.

2 Institute for Research in Biomedicine-Barcelona,08028-Barcelona, Spain. E-mail:

3CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, 08028-Barcelona, Spain

4Department of Chemistry, Faculty of Science, Alexandria UniversityP.O. Box 426, Ibrahimia, Alexandria 21321, Egypt. E-mail:

5 Department of Chemistry, College of Science, King Saud UniversityP.O. Box 2455,Riyadh11451, Saudi Arabia

6 School of Chemistry and Physics, University ofKwaZulu-Natal, Durban 4001, South Africa

7Department of Organic Chemistry, University of Barcelona, 08028-Barcelona, Spain

1- HPLC chromatogram of Z-Phg-Pro-NH2 experiments:

A linear gradient of 25–50% CH3CN/H2O and 0.1% TFA over 15 min was applied, with a flow rate of 1.0 mL/min and detection at 220 nm using a Phenomex C18 (3 μm, 4.6 × 50 mm) column, tR(LL) = 6.1 min, tR(DL) = 6.6 min, tR(Z-Phg-OH) = 8.5 min.

1-1- HOBt in 2-MeTHF

1-2- HOBt in CPME

1-3- HOAt in 2-MeTHF

1-4- HOAt in CPME

1-5- OxymaPure in 2-MeTHF

1-6- OxymaPure in CPME

1-7- K-Oxyma in DMF

1-8- K-Oxyma in THF

1-9- K-Oxyma in ACN

1-10-K-Oxyma in 2-MeTHF

1-11-K-Oxyma in CPME

1-12- Oxyma-B in 2-MeTHF

1-13- Oxyma-B in CPME

1-14- HBTU in 2-MeTHF

1-15- HBTU in CPME

1-16- HATU in 2-MeTHF

1-17- HATU in CPME

1-18- COMU in 2-MeTHF

1-19- COMU in CPME

2- HPLC chromatogram of solid-synthesis of H-Tyr-Aib-Aib-Phe-Leu-NH2using PS resin:

A Phenomex C18 (3μm, 4.6 × 50 mm) column, with a linear gradient of 20 to 40% of 0.1% TFA in CH3CN/0.1 %TFA in H2O over 15 min, flow rate = 1.0 mLmin–1, detection at 220 nm was used. The tR values for pentapepide and des-Aib were 6.7 min and 6.8 min, respectively.

2-1- HOBt in THF

2-2- HOBt in 2-MeTHF

2-3- HOBt in CPME

2-4- HOAt in THF

2-4- HOAt in 2-MeTHF

2-5- HOAt in CPME

2-6- OxymaPure in THF

2-7- OxymaPure in 2-MeTHF

2-8- OxymaPure in CPME

2-9- K-Oxyma in DMF

2-10- K-Oxyma in THF

2-11- K-Oxyma in 2-MeTHF

2-12- K-Oxyma in CPME

2-13- Oxyma-B in THF

2-14- Oxyma-B in 2-MeTHF

2-15- Oxyma-B in CPME

2-16- HBTU in 2-MeTHF

2-17- HATU in 2-MeTHF

2-18- COMU in 2-MeTHF

3- HPLC chromatogram of solid-synthesis of H-Tyr-Aib-Aib-Phe-Leu-NH2using ChemMatrix resin:

3-1- HOBt in 2-MeTHF

3-2- HOBt in CPME

3-3- HOAt in 2-MeTHF

3-4- HOAt in CPME

3-5- OxymaPure in 2-MeTHF

3-6- OxymaPure in CPME

3-7- K-Oxyma in DMF

3-8- K-Oxyma in THF

3-9- K-Oxyma in ACN

3-10- K-Oxyma in 2-MeTHF

3-11- K-Oxyma in CPME

3-12- Oxyma-B in 2-MeTHF

3-13- Oxyma-B in CPME