Efficient Fmoc-Protected Amino Ester Hydrolysis Using Green Calcium(II) Iodide as a Protective Agent

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 9; p. 2788
• Main Authors: Binette, Renaud, Desgagné, Michael, Theaud, Camille, Boudreault, Pierre-Luc
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.04.2022; MDPI
• Subjects: amino acid; Amino acids; ester hydrolysis; Fmoc; green chemistry; medicinal chemistry; NMR; Nuclear magnetic resonance; solid-phase synthesis; Solvents; United States > US; ester hydrolysis; Fmoc; amino acid; green chemistry; solid-phase synthesis; medicinal chemistry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27092788

In order to modify amino acids, the C-terminus carboxylic acid usually needs to be protected, typically as a methyl ester. However, standard cleavage of methyl esters requires either highly basic or acidic conditions, which are not compatible with Fmoc or acid-labile protecting groups. This highlights the need for orthogonal conditions that permit selective deprotection of esters to create SPPS-ready amino acids. Herein, mild orthogonal ester hydrolysis conditions are systematically explored using calcium(II) iodide as a protective agent for the Fmoc protecting group and optimized for a broad scope of amino esters. Our optimized reaction improved on the already known trimethyltin hydroxide, as it produced better yields with greener, inexpensive chemicals and a less extensive energy expenditure.