carba‐Nucleopeptides (cNPs): A Biopharmaceutical Modality Formed through Aqueous Rhodamine B Photoredox Catalysis

Abstract

Exchanging the ribose backbone of an oligonucleotide for a peptide can enhance its physiologic stability and nucleic acid binding affinity. Ordinarily, the eneamino nitrogen atom of a nucleobase is fused to the side chain of a polypeptide through a new CÀ N bond. The discovery of CÀ C linked nucleobases in the human transcriptome reveals new opportunities for engineering nucleopeptides that replace the traditional CÀ N bond with a non-classical CÀ C bond, liberating a captive nitrogen atom and promoting new hydrogen bonding and π-stacking interactions. We report the first late-stage synthesis of CÀ C linked carba-nucleopeptides (cNPs) using aqueous Rhodamine B photoredox catalysis. We prepare brand-new cNPs in batch, in parallel, and in flow using three long-wavelength photochemical setups. We detail the mechanism of our reaction by experimental and computational studies and highlight the essential role of diisopropylethylamine as a bifurcated twoelectron reductant.

Photo‐triggered Intramolecular Radical Tandem Regioselective Alkylation/Cyclization of 1,6‐Dienes with Redox‐Active Esters Enabled by an EDA Complex

“…During the past decade, photoredox catalysis has gained enormous interest in organic chemistry due to its non-toxic feature, environment-friendliness and mild condition. [9] As a result, great effort has been focused on this field. Traditionally, photocatalysts such as expensive metal complexes or elaborate organic dyes, are essential for initiation step of photochemical transformation via single electron transfer (SET) or energy transfer (EnT) process.…”