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

• DOI: 10.1021/acs.orglett.3c00766
• Publication Date: 2023-04-27T12:25:08Z
• Authors: Liangliang Song; Zhenwei Lv; Yan Li; Kui Zhang; Erik V. Van der E...; Lingchao Cai
• Keywords: Annulation; Conjugate; Residue (chemistry)

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- site-selectivity, broad scope including substrates bearing unprotected Trp Tyr, free Ser Gln, Met residues. The conjugates also display good fluorescent properties with maximum emission wavelengths up to 460 nm. Importantly, preliminary antifungal activity studies indicate that peptide–isoquinolone show potential activities toward crop forest pathogenic fungi, which conjugate Tyr residue exhibits much better B. cinerea Pers. C. chrysosperma than positive control.