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Updated: Jul 10, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
A Tight Contact: The Expanding Application of Salicylaldehydes in Lysine-Targeting Covalent Drugs
Mattia Mason1, Laura Belvisi1, Luca Pignataro1
1Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milan, Italy.
Abstract:
The installation of aldehydes into synthetic protein ligands is an efficient strategy to engage protein lysine residues in remarkably stable imine bonds and augment the compound affinity and selectivity for their biological targets. The high frequency of lysine residues in proteins and the reversibility of the covalent ligand-protein bond support the application of aldehyde-bearing ligands, holding promises for their future use as drugs. This review highlights the increasing exploitation of salicylaldehyde modules in various classes of protein binders, aimed at the reversible-covalent engagement of lysine residues.
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The acidic strength of hydrocarbons follows the order: Alkynes > Alkenes > Alkanes. The strength of an acid is commonly expressed in units of pKa — the lower the pKa, the stronger the acid. Among the hydrocarbons, terminal alkynes have lower pKa values and are, therefore, more acidic. For example, the pKa values for ethane, ethene, and acetylene are 51, 44, and 25, respectively, as shown here.
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Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
α-Alkylation of Ketones via Enolate Ions
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