Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines

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Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines. / Stuhr-Hansen, Nicolai; Bork, Nicolai; Strømgaard, Kristian.

In: Organic & Biomolecular Chemistry, Vol. 12, No. 30, 14.08.2014, p. 5745-51.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Stuhr-Hansen, N, Bork, N & Strømgaard, K 2014, 'Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines', Organic & Biomolecular Chemistry, vol. 12, no. 30, pp. 5745-51. https://doi.org/10.1039/c4ob00073k

APA

Stuhr-Hansen, N., Bork, N., & Strømgaard, K. (2014). Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines. Organic & Biomolecular Chemistry, 12(30), 5745-51. https://doi.org/10.1039/c4ob00073k

Vancouver

Stuhr-Hansen N, Bork N, Strømgaard K. Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines. Organic & Biomolecular Chemistry. 2014 Aug 14;12(30):5745-51. https://doi.org/10.1039/c4ob00073k

Author

Stuhr-Hansen, Nicolai ; Bork, Nicolai ; Strømgaard, Kristian. / Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines. In: Organic & Biomolecular Chemistry. 2014 ; Vol. 12, No. 30. pp. 5745-51.

Bibtex

@article{718272f0b8a14b8a80a4a89308158491,
title = "Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines",
abstract = "The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities of thiophenol (PhSH) in a slurry of disodium hydrogen phosphate in dry DMF. Quantitative conversions into the resulting amide were observed within a few hours in the presence of equimolar amounts of thiophenol. Ab initio calculations showed that the reaction mechanism in DMF is similar to the well-known aqueous reaction mechanism. The energy barrier of the catalyzed amidation reaction is approximately 40 kJ mol(-1) lower than the non-catalyzed amidation reaction. At least partially this can be explained by a hydrogen bond from the amine to the π-electrons of the thiophenol, stabilizing the transition state in the aromatic thioester amidation reaction. Under similar conditions, cysteine-free ligation was achieved by coupling a fully side-chain protected 15 amino acid phosphopeptide thioester to the free N-terminal of a side-chain protected 9 amino acid peptide producing the corresponding 24 amino acid phosphopeptide.",
author = "Nicolai Stuhr-Hansen and Nicolai Bork and Kristian Str{\o}mgaard",
year = "2014",
month = "8",
day = "14",
doi = "10.1039/c4ob00073k",
language = "English",
volume = "12",
pages = "5745--51",
journal = "Organic & Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "30",

}

RIS

TY - JOUR

T1 - Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines

AU - Stuhr-Hansen, Nicolai

AU - Bork, Nicolai

AU - Strømgaard, Kristian

PY - 2014/8/14

Y1 - 2014/8/14

N2 - The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities of thiophenol (PhSH) in a slurry of disodium hydrogen phosphate in dry DMF. Quantitative conversions into the resulting amide were observed within a few hours in the presence of equimolar amounts of thiophenol. Ab initio calculations showed that the reaction mechanism in DMF is similar to the well-known aqueous reaction mechanism. The energy barrier of the catalyzed amidation reaction is approximately 40 kJ mol(-1) lower than the non-catalyzed amidation reaction. At least partially this can be explained by a hydrogen bond from the amine to the π-electrons of the thiophenol, stabilizing the transition state in the aromatic thioester amidation reaction. Under similar conditions, cysteine-free ligation was achieved by coupling a fully side-chain protected 15 amino acid phosphopeptide thioester to the free N-terminal of a side-chain protected 9 amino acid peptide producing the corresponding 24 amino acid phosphopeptide.

AB - The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities of thiophenol (PhSH) in a slurry of disodium hydrogen phosphate in dry DMF. Quantitative conversions into the resulting amide were observed within a few hours in the presence of equimolar amounts of thiophenol. Ab initio calculations showed that the reaction mechanism in DMF is similar to the well-known aqueous reaction mechanism. The energy barrier of the catalyzed amidation reaction is approximately 40 kJ mol(-1) lower than the non-catalyzed amidation reaction. At least partially this can be explained by a hydrogen bond from the amine to the π-electrons of the thiophenol, stabilizing the transition state in the aromatic thioester amidation reaction. Under similar conditions, cysteine-free ligation was achieved by coupling a fully side-chain protected 15 amino acid phosphopeptide thioester to the free N-terminal of a side-chain protected 9 amino acid peptide producing the corresponding 24 amino acid phosphopeptide.

U2 - 10.1039/c4ob00073k

DO - 10.1039/c4ob00073k

M3 - Journal article

C2 - 24967660

VL - 12

SP - 5745

EP - 5751

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1477-0520

IS - 30

ER -

ID: 120130682