Construction of Peptide–Isoquinolone Conjugates via Rh(III)-Catalyzed C–H Activation/Annulation

Herein, we disclose a Rh(III)-catalyzed C–H activation/annulation reaction for the derivatization of Lys-based peptides, in situ affording diverse peptide-isoquinolone conjugates. This approach features racemization-free conditions, high atom- and step-economy, excellent chemo- and site-selectivity, and broad scope including substrates bearing unprotected Trp and Tyr, free Ser and Gln, and Met residues. The peptide-isoquinolone conjugates also display good fluorescent properties with maximum emission wavelengths up to 460 nm. Importantly, preliminary antifungal activity studies indicate that peptide–isoquinolone conjugates show potential activities toward crop and forest pathogenic fungi, in which the peptide–isoquinolone conjugate bearing unprotected Tyr residue exhibits much better antifungal activities toward B. cinerea Pers. and C. chrysosperma than the positive control.