K-Oxyma: A strong acylation-promoting, 2-ctc resin-friendly coupling additive

Here we present a new formulation of the recently introduced OxymaPure additive for peptide bond formation, in which the N-hydroxylamine group is replaced by a potassium salt. The complete suppression of its acidity converts K-Oxyma into the most suitable coupling choice when peptides are assembled on highly acid-labile solid-supports. The coupling efficiency and diminished prospects for epimerization are conserved relative to OxymaPure. In addition, K-Oxyma displays excellent solubility in a variety of organic solvents and undergoes safer decomposition than classical 1-hydroxybenzotriazole additives. A new oxime-based coupling additive is introduced for peptide bond formation. The potassium salt of OxymaPure, K-Oxyma, is readily obtained from commercially available precursors. Unlike common N-hydroxylamines, K-Oxyma is compatible with extremely acid-labile solid-supports, displays excellent solubility, minimizes epimerization, and enhances coupling efficiency relative to OxymaPure.