Multigram-Scale Synthesis of Short Peptides via a Simplified Repetitive Solution-Phase Procedure
Abstract
A rapid repetitive solution-phase synthesis of peptides is described. The procedure involves coupling of amino acids and peptide acids, instead of the usual amino esters and peptide esters, to slight excesses of pentafluorophenyl active esters in a THF/water solvent mixture. Due to their poor solubility, peptide acid intermediates are easily isolated in high purity by acidification under controlled conditions and removal of excess active esters by selective extraction. Contrary to modern repetitive solution-phase peptide synthesis procedures, our approach does not require time-consuming neutralization reactions and reduces significantly the number of operation units that are necessary to obtain peptide intermediates. Efficiency of the method was demonstrated by the rapid synthesis of short hydrophobic and hydrophilic peptides, the antimalarial cycloheptapeptide mahafacyclin B, and a protected form of the hydrophilic pentapeptide GRGDS.
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While some optimizations have been performed, a practical strategy for N → C peptide synthesis using unprotected amino acids remains unavailable.
“While some optimizations have been performed, practical strategy remains unavailable.21”
From Ynamide Coupling Reagents: Origin and Advances (2024) · cites this paper as [21]
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- Authors
- Meneses, C., Nicoll, S. L., & Trembleau, L.
- Affiliations
- University of Aberdeen (GB)
- ORCID
- Trembleau, Laurent
- Venue
- The Journal of Organic Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-12-31
- Volume
- 75
- Issue
- 3
- Pages
- 564-569
- ISSN
- 0022-3263 (ISSN-L)
- 1520-6904
- OpenAlex
- W2036602792
- Cited by
- 22
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Organic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Synthetic Organic Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- MeSH terms
- Amino Acid Sequence, Esters, Oligopeptides, Peptides, Peptides, Cyclic, Solubility, Solutions, Solvents, Stereoisomerism, Hydrophobic and Hydrophilic Interactions
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