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-Faham; Fernando Albericio

doi:10.1007/s00726-015-2095-x

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

Amino Acids. 2016 Feb;48(2):419-26. doi: 10.1007/s00726-015-2095-x. Epub 2015 Sep 24.

Authors

Yahya E Jad¹, Gerardo A Acosta^{2

3}, Sherine N Khattab⁴, Beatriz G de la Torre¹, Thavendran Govender¹, Hendrik G Kruger¹, Ayman El-Faham^{5

6}, Fernando Albericio^{7

8

9

10

11

12}

Affiliations

¹ Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa.
² Institute for Research in Biomedicine-Barcelona, 08028, Barcelona, Spain.
³ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, 08028, Barcelona, Spain.
⁴ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria, 21321, Egypt.
⁵ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria, 21321, Egypt. aymanel_faham@hotmail.com.
⁶ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. aymanel_faham@hotmail.com.
⁷ Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa. albericio@irbbarcelona.org.
⁸ Institute for Research in Biomedicine-Barcelona, 08028, Barcelona, Spain. albericio@irbbarcelona.org.
⁹ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, 08028, Barcelona, Spain. albericio@irbbarcelona.org.
¹⁰ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia. albericio@irbbarcelona.org.
¹¹ School of Chemistry and Physics, University of KwaZulu-Natal, Durban, 4001, South Africa. albericio@irbbarcelona.org.
¹² Department of Organic Chemistry, University of Barcelona, 08028, Barcelona, Spain. albericio@irbbarcelona.org.

PMID: 26403847
DOI: 10.1007/s00726-015-2095-x

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

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Design
Furans / chemistry*
Methyl Ethers / chemistry*
Peptides / chemical synthesis*
Solid-Phase Synthesis Techniques*

Substances

Furans
Methyl Ethers
Peptides
2-methyltetrahydrofuran