Proximity-Induced Ligation and One-Pot Macrocyclization of 1,4-Diketone-Tagged Peptides Derived from 2,5-Disubstituted Furans upon Release from the Solid Support

1,4-Dione-containing peptides are generated during the cleavage of 2,5-disubstituted furan-containing systems. The generated electrophilic systems then react with a-effect nucleophiles, following a Paal-Knorr-like mechanism, for the generation of macrocyclic peptides, occurring after simple resuspension of the crude peptide in water. Conveniently, the in situ generation of the electrophile from a stable furan ring avoids the complications associated with the synthesis of carbonyl-containing peptides. Detailed investigation of the reaction characteristics was first performed on supramolecular coiled-coil systems.

Automated summary

1,4-Dione-containing peptides are generated from the cleavage of 2,5-disubstituted furan-containing systems. The generated electrophilic systems react with a-effect nucleophiles, following a Paal-Knorr-like mechanism, to form macrocyclic peptides after resuspension in water. Detailed investigation of the reaction characteristics was performed on supramolecular coiled-coil systems.