Nature paper reports general synthesis route for tryptophan-crosslinked macrocyclic peptides

The wire

1. 01Researchers describe a rhodium-catalysed intramolecular transannular macrocyclization using a dual-function nucleophilic pyridyl directing group that enables ortho-metalation and carbon–nitrogen bond formation in complex peptides.
2. 02Tryptophan-crosslinked macrocycles are natural products with reported therapeutic properties, and no simple broadly applicable total synthesis route existed; chemistry like this underpins the macrocyclic peptide drug pipeline.
3. 03The work is synthetic chemistry only, demonstrated on pharmacophores rather than finished drug candidates, with no biological or clinical data reported.

From the source

A general synthesis of tryptophan-crosslinked macrocyclic peptides enabled by a dual-functional directing group

Tryptophan-crosslinked macrocyclic peptides have recently emerged as an exciting class of natural products with intricate structures and therapeutic properties. Although their biosynthesis and biological functions have been explored, simple and broadly applicable chemical methods for their total synthesis are not available. Here we describe a general approach for the synthesis of these rigid and c