Click Macrocyclization

Significance

Cyclic tetra-, penta-, hexa-, and heptapeptides 5a-e were prepared via solid-phase click macrocyclization. Thus, resin-bound peptides 3a-e were prepared from a 2-chlorotrityl resin-supported alkyne 1 via a parallel split-split synthesis. The click macrocyclization of 3b-e with CuBr followed by cleavage from the polymer resin afforded the corresponding macromonomers 5b-e in 20-27% yield (from 3) with small amounts of cyclodimers 6b-e and cyclooligomers.