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Amino Acids

, Volume 48, Issue 2, pp 419–426 | Cite as

2-Methyltetrahydrofuran and cyclopentyl methyl ether for green solid-phase peptide synthesis

  • Yahya E. Jad
  • Gerardo A. Acosta
  • Sherine N. Khattab
  • Beatriz G. de la Torre
  • Thavendran Govender
  • Hendrik G. Kruger
  • Ayman El-FahamEmail author
  • Fernando AlbericioEmail author
Original Article

Abstract

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined. We concluded that the use of 2-MeTHF with combination of DIC/OxymaPure gave the lowest racemization level during stepwise synthesis of Z-Phg-Pro-NH2 and the highest purity during SPPS of Aib-enkephalin pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH2).

Keywords

Green solvents Solid-phase peptide synthesis Peptide synthesis 2-methyltetrahydrofuran Cyclopentyl methyl ether 

Abbreviations

ACN

Acetonitrile

ACS GCIPR

American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable

COMU

1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholinomethylene)]methanaminium hexafluorophosphate

CPME

Cyclopentyl methyl ether

DCM

Dichloromethane

DIC

N,N′-diisopropylcarbodiimide

DIEA

N,N-diisopropylethylamine

DMF

N,N-dimethylformamide

HATU

N-[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]-pyridin-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide

HBTU

N-[(1H-benzotriazol-1-yl)(dimethylamino)-methylene]-N-methylmethanaminium hexafluorophosphate N-oxide

HOAt

1-Hydroxy-7-azabenzotriazole

HOBt

1-Hydroxybenzotriazole

2-MeTHF

2-Methyltetrahydrofuran

NMP

N-methyl-2-pyrrolidone

Oxyma-B

5-(Hydroxyimino)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione

OxymaPure

Ethyl 2-cyano-2-(hydroxyimino)acetate

PS

Polystyrene

THF

Tetrahydrofuran

Notes

Acknowledgments

This work was funded in part by the following: the National Research Foundation (NRF) and the University of KwaZulu-Natal (South Africa); the CICYT (CTQ2012-30930), the Generalitat de Catalunya (2014 SGR 137), and the Institute for Research in Biomedicine Barcelona (IRB Barcelona) (Spain). In addition, the authors thank the Deanship of Scientific Research at King Saud University for partially funding this work through research group No. RGP-234 (Saudi Arabia). Finally, we thank Dr Karine Salim (Pcas) for the generous gift of ChemMatrix resin and Yoav Luxembourg (Luxembourg Bio Technologies Ltd) for his continuous support of this study.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.

Supplementary material

726_2015_2095_MOESM1_ESM.docx (2.5 mb)
Supplementary material 1 (DOCX 2608 kb)

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • 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
    Email author
  • Fernando Albericio
    • 1
    • 2
    • 3
    • 5
    • 6
    • 7
    Email author
  1. 1.Catalysis and Peptide Research Unit, School of Health SciencesUniversity of KwaZulu-NatalDurbanSouth Africa
  2. 2.Institute for Research in Biomedicine-BarcelonaBarcelonaSpain
  3. 3.CIBER-BBNNetworking Centre on Bioengineering, Biomaterials and NanomedicineBarcelonaSpain
  4. 4.Department of Chemistry, Faculty of ScienceAlexandria UniversityAlexandriaEgypt
  5. 5.Department of Chemistry, College of ScienceKing Saud UniversityRiyadhSaudi Arabia
  6. 6.School of Chemistry and PhysicsUniversity of KwaZulu-NatalDurbanSouth Africa
  7. 7.Department of Organic ChemistryUniversity of BarcelonaBarcelonaSpain

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