A biomolecule-compatible visible-light-induced azide reduction from a DNA-encoded reaction-discovery system

Abstract

Using a system that accelerates the serendipitous discovery of new reactions by evaluating hundreds of DNA-encoded substrate combinations in a single experiment, we explored a broad range of reaction conditions for new bond-forming reactions. We discovered reactivity that led to a biomolecule-compatible, Ru(II)-catalyzed, visible light-induced azide reduction reaction. In contrast with current azide reduction methods, this reaction is highly chemoselective and is compatible with alcohols, phenols, acids, alkenes, alkynes, aldehydes, alkyl halides, alkyl mesylates, and disulfides. The remarkable functional group compatibility and mild conditions of this reaction enabled azide reduction to be performed on nucleic acid and oligosaccharide substrates without the detectable occurrence of side reactions. The reaction was also performed in the presence of a protein enzyme without loss of enzymatic activity, in contrast with two commonly used azide reduction methods. The visible light dependence of this reaction provides a means of photouncaging functional groups such as amines and carboxylates on biological macromolecules without using UV irradiation.

The Development of Visible‐Light Photoredox Catalysis in Flow

“…The first reaction examined was the reduction of azides to amines first developed by Liu and co-workers (Scheme 1A). [8] The yield for the reduction of 1 to 2 was improved from 70 to 89%, while the reaction time was reduced 12-fold when comparing batch to flow. The flow conditions were next applied to the reductive ring opening of epoxychalcone 3 (Scheme 1B).…”

Synthesis, structure and in vitro cytostatic activity of ferrocene—Cinchona hybrids

“…In this regard it is also important to mention that in preliminary studies hybrids 4a-d proved to be highly active against MDR cancer stem cell lines. 21 We also disclosed structure activity relationship data (SAR) demonstrating the importance of chalcone moiety as well as the cytostatic effect of an alkynetethered ferrocene-cinchona hybrid (16b). The surprising in vitro activity of (E)-3-(2-azidophenyl)-1-(ferrocenyl)prop-2-en-1-one (2), characterized by pronounced dependence on substitution pattern, might initiate a conceptually novel approach in the search for a novel class of active molecules.…”

Visible‐Light Sensitization of Vinyl Azides by Transition‐Metal Photocatalysis

“…8 Liu has recently reported visible light induced photoreduction of aryl azides using Ru(bpy) 3 2+ as a photocatalyst (Scheme 1, eq 1). 9 The key intermediate in this reaction, however, was proposed to be a nitrene radical anion generated by one-electron reduction of the azide, and these intermediates do not exhibit the characteristic reactivity of neutral nitrenes. 10 We wondered, therefore, if we might be able to access the powerful C-N bond-forming reactivity of nitrenes using visible As a test of this hypothesis, we investigated the photocatalytic transformation of dienyl azides into pyrroles (Scheme 1, eq 2).…”