Environmentally Friendly SPPS II: Scope of Green Fmoc Removal Protocol Using NaOH and Its Application for Synthesis of Commercial Drug Triptorelin.

The Journal of Organic Chemistry
Adam PřibylkaEva Schütznerová

Abstract

With the growing necessity to consider environmental impacts when synthesizing peptide-based drugs and to expand upon the recently published short communication report, we herein present a thorough evaluation of a green Fmoc removal protocol. Our protocol avoids the use of hazardous components (using piperidine as a base and dichloromethane (DCM) and N,N-dimethylformamide (DMF) as solvents) and relies on the utilization of the green mineral base NaOH in combination with the greener solvent 2-methyltetrahydrofuran (2-MeTHF) mixed with MeOH. For the original Fmoc removal cocktail (solvents ratio of 1:1), we evaluated the impact of quality/purity of the used 2-MeTHF, scale-up, ratio of 2-MeTHF/MeOH, utilized hydroxide, temperature, and reaction time. An alternative 3:1 protocol was examined using various amino acids, and only Gly required the optimization of the Fmoc removal cocktail composition. The optimized protocol used to remove Fmoc from Gly residue was proved by the synthesis of Leu-enkephalin. We also investigated the stability of the conventional amino acid side-chain-protecting groups, t-Bu, Boc, Trt, and Pbf, and the formation of aspartimide as an undesirable side reaction that occurs during Fmoc solid-phase peptide syn...Continue Reading

References

Jan 1, 1980·International Journal of Peptide and Protein Research·C D ChangJ D Haug
Jan 1, 1994·Methods in Molecular Biology·G B Fields
May 14, 1999·Journal of Peptide Science : an Official Publication of the European Peptide Society·C ChivaF Albericio
Oct 6, 2001·Journal of Peptide Science : an Official Publication of the European Peptide Society·A K TicklerJ D Wade
Jun 20, 2003·Nature Reviews. Drug Discovery·Brian L Bray
Feb 18, 2004·Current Pharmaceutical Biotechnology·Thomas BruckdorferFernando Albericio
Jan 11, 2005·Journal of Combinatorial Chemistry·Nikos ZinierisNikolas Ferderigos
Mar 15, 2006·Journal of Combinatorial Chemistry·John Hachmann, Michal Lebl
Jun 8, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Keiko HojoKoichi Kawasaki
Nov 1, 2007·Expert Opinion on Investigational Drugs·Andrea C WilsonCraig S Atwood
Apr 15, 2009·Chemical Reviews·Albert Isidro-LlobetFernando Albericio
May 1, 2009·Future Medicinal Chemistry·Aikaterini A ZompraFernando Albericio
Aug 27, 2011·Chemical Reviews·Ayman El-Faham, Fernando Albericio
Jul 27, 2012·Current Medicinal Chemistry·D GoodwinI Toth
Aug 25, 2012·Future Medicinal Chemistry·Fernando Albericio, Hendrik G Kruger
Dec 21, 2012·Chemical Biology & Drug Design·David J CraikDavid Price
Jun 4, 2013·Drug Discovery Today·Allan A Kaspar, Janice M Reichert
Aug 24, 2013·Current Protein & Peptide Science·Kelly Cristina Leite MulderNádia Skorupa Parachin
Dec 3, 2014·Drug Discovery Today·Keld Fosgerau, Torsten Hoffmann
Jan 8, 2015·Organic & Biomolecular Chemistry·Yahya E JadFernando Albericio
Jun 30, 2015·Chemical Reviews·Angeles FarránRobert J Linhardt
Jan 21, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Raymond BehrendtJohn Offer
Nov 18, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Omar F LunaFanny Guzmán
Jul 20, 2017·Bioorganic & Medicinal Chemistry·Jolene L Lau, Michael K Dunn
May 8, 2018·Pharmaceuticals·Othman Al MusaimiFernando Albericio
Jan 27, 2019·Chemistry, an Asian Journal·Kyriakos G Varnava, Vijayalekshmi Sarojini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Related Papers

Journal of Peptide Science : an Official Publication of the European Peptide Society
Raymond BehrendtJohn Offer
Methods in Enzymology
D A Wellings, E Atherton
Methods in Molecular Biology
Lena MünzkerPaul R Hansen
Methods in Molecular Biology
Paul R Hansen, Alberto Oddo
Journal of Combinatorial Chemistry
John Hachmann, Michal Lebl
© 2022 Meta ULC. All rights reserved