American Chemical Society
jo4c00048_si_001.pdf (9.24 MB)

Ru(II)-Catalyzed C(sp2)–H Activation Annulation: Synthesis of Fluorescent Benzoisoquinolonyl Acetate/Peptides from N‑Arylamides and Ethyne at Room Temperature

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journal contribution
posted on 2024-05-16, 03:43 authored by Manish K. Gupta, Ankita Panda, Nagendra K. Sharma
Benzoisoquinolones are aryl ring extended isoquinolinone derivatives, which are constituents of alkaloid natural products. This report describes the synthesis of novel benzoisoquinolone amino acid/peptide derivatives from the respective N-aryl amino esters/peptides through Ru-catalyzed C­(sp2)–H annulation at room temperature. The N-terminal amide acts as an intrinsic directing group and coordinates with the active Ru­(II) catalyst for the C–H bond activation and annulation of the aryl ring to produce benzoisoqunolone derivatives. Importantly, these benzoisoquinolinones exhibit fluorescence (QY ∼35%) in protic polar solvents, possibly due to charge transfer, and exhibit cell internalization to the cell nucleus without any significant cytotoxicity to human cell lines (HEK293T). Hence, our results are exceptional to transform standard amino acids/peptides into fluorescent peptides at room temperature in the late stage, which could be applicable for tracking specific target peptides by fluorescence microscopy.