Solvent‐Free Synthesis of Peptides

CHAPTER 10. Technical Implications of Organic Syntheses in Ball Mills

“…through a maximum. 29,88 As this is typical for a quadratic function it is reasonable from mathematical point of view, but it is also explainable from chemical viewpoint. High energy impacts may distort the chemical equilibrium, favouring unwanted side reactions, resulting in a decrease of the mentioned variables.…”

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

“…Indeed, liquid reaction mixtures enable efficient agitation when using a conventional batch reactor equipped with either magnetic stirring bar or impeller, and automated handling such as pumping and filtration. Since Lamaty and co-workers have shown in their seminal work that peptide synthesis could be performed in a ball-mill (BM) [9], various solvent-free or solvent-less peptide synthesis strategies have been developed [10][11][12][13][14][15][16][17]. While these approaches enable to circumvent the use of toxic solvents and bases [18][19][20], no comparison between ballmilling and conventional approaches was performed, discussed and communicated.…”

CHAPTER 6. Amino Acids and Peptides in Ball Milling

“…40 Initial investigations were carried out on the coupling of the Boc-protected phenylalanine N-carboxyanhydride (Boc-Phe-NCA) with alanine methyl ester hydrochloride salt (HCl Á H-Ala-OMe) in the presence of NaHCO 3 in a vibrating ball-mill (Scheme 6.13).…”

“…Organic solventfree recovery and purification have been a scarcely studied theme in fine organic chemistry, but promising methods have been published recently. 38,40,[48][49][50][51] Mechanochemical peptide syntheses would gain even more interest in the organic chemist's community if solutions addressing this challenge would emerge.…”