Integration of C-Acylation in the Solid-Phase Synthesis of Peptides and Peptidomimetics employing Meldrum’s Acid, Phosphorus and Sulfur Ylides

Modification of native peptides to peptidomimetics is an important goal in medicinal chemistry and requires in many cases the integration of C-acylation steps involving amino acids with peptide synthesis. Many classical C-acylation protocols involving Claisen condensations or the use of ylides are not compatible with peptide synthesis, mostly due to the requirement of strong bases leading to epimerization or deprotection of peptides. Meldrum’s acid as well as several specific phosphorus and sulfur ylides, however, are acidic enough to provide reactive C-nucleophiles at mildly basic conditions tolerated during peptide synthesis. This review provides an overview of peptide-compatible C-acylations of Meldrum´s acid, phosphorus and sulfur ylides and their application in the medicinal chemistry of peptides.

Mild synthesis of isoxazoline derivatives via an efficient [4 + 1] annulation reaction of transient nitrosoalkenes and sulfur ylides

An efficient [4 + 1] annulation between α-bromooximes and sulfur ylides via in situ generation of nitrosoalkenes under mild basic reaction conditions has been developed, providing an expeditious and scalable approach to synthesize biologically interesting isoxazoline derivatives with good to excellent yields.