Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

Yeboue, Yves; Rguioueg, Nadia; Subra, Gilles; Martínez, Jean; Lamaty, Frédéric; Métro, Thomas‐Xavier

doi:10.1002/ejoc.202100839

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…In response to these issues, Métro and co-workers [115] assessed the capacity of ball mills to reduce or eliminate the propensity for epimerization during the peptide coupling, comparing these results to those obtained with classical approaches in solution (Table 7). In addition, mechanosynthesis was developed using two different target amino acids: phenyl glycine (H-Phg-OH), known for its increased tendency for racemization, and isoleucine (H-Ile-OH), which has a significant…”

Section: Mechanochemical Formation Of Higher-ordered Peptide Structuresmentioning

confidence: 99%

Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

et al. 2022

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Mechanochemical transformations have made chemists enter unknown territories, forcing a different chemistry perspective. While questioning or revisiting familiar concepts belonging to solution chemistry, mechanochemistry has broken new ground, especially in the panorama of organic synthesis. Not only does it foster new "thinking outside the box", but it also has opened new reaction paths, allowing to overcome the weaknesses of traditional chemistry exactly where the use of well-established solution-based methodologies rules out progress. In this Review, the reader is introduced to an intriguing research subject not yet fully explored and waiting for improved understanding. Indeed, the study is mainly focused on organic transformations that, although impossible in solution, become possible under mechanochemical processing conditions, simultaneously entailing innovation and expanding the chemical space.This publication is part of a joint Special Collection of Chemistry-Methods and ChemSusChem including invited contributions focusing on "Methods and Applications in Mechanochemistry". Please visit chemsuschem.org/ collections to view all contributions.

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Section: Mechanochemical Formation Of Higher-ordered Peptide Structuresmentioning

confidence: 99%

Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

et al. 2022

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“…69 The risk of epimerization represents a severe hurdle in amide coupling. 70 In this regard, Métro and co-workers 71 examined the potential of ball milling to eliminate epimerization during peptide coupling. In the process, it was observed that the mechanochemical procedure required only one-third of this reaction time, probably as consequence of higher concentration of the reagents in the ball mill, that shortens reaction times relative to the corresponding reaction in solution.…”

Section: Amino Acid and Peptide Mechanosynthesismentioning

confidence: 99%

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

Juaristi

Avila‐Ortiz

2023

Synthesis

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Although known for millenia, it is only recently that mechanochemistry has caught serious attention by many chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques has been recorded. This short review discusses the circumstances that led to such renaissance, highlighting the present intense interest in so-called green chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates, and the finding of the profound influence that additives can have on mechanochemically activated reactions. The core of this account focuses on salient developments in synthetic organic chemistry, especially in amino acid and peptide mechanosynthesis, the successful employment of mechanochemical activation in combination with asymmetric organocatalysis, the promising combination of mechanochemical activation with enzymatic and whole cell biocatalysis, and the remarkable achievement of multicomponent selective reactions via complex, multistep reaction pathways. The final section is dedicated to comment on some pending tasks in the area, such as scaling-up of milling processes to be of practical use in the chemical industry, the requirement of easier and more efficient control of reaction parameters and monitoring devices, and consequently the careful analysis of additional procedures for a proper understanding of mechanochemical phenomena.

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“…[34] In the context of small organic molecules chemistry, sustainable methods for the formation of amides are particularly required considering the high environmental impact of classical methods involving low atom economy activating agents such as HATU or EDCI. Greener approaches involving mechanochemistry, [35][36][37] neat reactions [38] or catalysis [39][40][41][42][43] have also been recently developed. The nature of the solvents used is also an important parameter and amide synthesis in water represents an alternative to highly toxic and hazardous solvents that are commonly used.…”

Section: Introductionmentioning

confidence: 99%

A Catalytic Approach for the Synthesis of Peptide−Oligonucleotides Conjugates in Aqueous Solution or On‐Column

Gras,

Adler,

Smietana

2024

Chemistry A European J

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Peptide–oligonucleotide conjugates (POCs) are covalent architectures composed of a DNA or RNA molecules linked to a peptide. These constructs have found widespread applications ranging from hybrid nanomaterials to gene‐targeted therapies. Considering the important role of POCs, a new catalytic approach for their preparation is reported here, that could be applied either on solid support in anhydrous media, or post‐synthetically in aqueous buffer. Single amino acids, peptides and cell penetrating peptides (CPPs) were conjugated to various oligo(ribo)nucleotides with high conversions and good isolated yields. The applicability of the method was demonstrated on more than 35 examples including an analogue of a commercial therapeutic oligonucleotide. Other conjugation partners, such as deoxycholic acid and biotin were also successfully conjugated to oligonucleotides. To highlight the potential of this catalytic approach, these conditions have been applied to iterative processes, which is of high interest for the development of DNA‐Encoded Libraries.

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Gram‐Scale Synthesis of a Hexapeptide by Fragment Coupling in a Ball Mill

Cited by 8 publications

References 35 publications

Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

A Catalytic Approach for the Synthesis of Peptide−Oligonucleotides Conjugates in Aqueous Solution or On‐Column

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