Peptide macrocycles are widely used in fields ranging from medicinal chemistry to
materials science. Efficient chemical methods for the synthesis of cyclic peptides
with novel three-dimensional structures are highly desired to facilitate the development
of this unique class of compounds. However, the range of methods available for constructing
peptide macrocycles is limited compared with that for small molecules. We recently
developed new methods for synthesizing highly constrained cyclic peptides with C–C
crosslinks through Pd-catalyzed C–H activation reactions. These methods use endogenous
backbone amides as directing groups and, therefore, have the potential for use in
late-stage functionalization of peptide natural products.
Key words
cyclic peptides - peptidomimetics - palladium catalysis - C–H activation - macrocyclization
- peptide stapling
