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Abstract We present the synthesis, properties, and imaging applications of a new class of diazaborine‐based probes (Peroxynitrite Probe‐1,PNP‐1) for selective peroxynitrite (ONOO⁻) imaging in live cells.PNP‐1features a diazaborine‐based reaction motif that provides excellent discrimination between H₂O₂and ONOO⁻, solving a persistent challenge of organoboron‐based fluorescent probes for oxidative metabolite imaging. We demonstrate the utility ofPNP‐1to detect endogenously produced ONOO⁻in live RAW 264.7 macrophages by fluorescence microscopy, with probe selectivity confirmed with inhibition of NADPH oxidases and nitric oxide synthase, the requisite enzymatic machinery for ONOO⁻production. Co‐localization studies unexpectedly reveal preferential mitochondrial localization, which we show is dependent on the naphthalimide scaffold. Taken together, our results show that diazaborines are a novel motif for selective ONOO⁻reactivity, positioning them for incorporation into other ONOO⁻‐specific chemical biology tools. 

Abstract Biocatalytic processes are highly selective and specific. However, their utility is limited by the comparatively narrow scope of enzyme‐catalysed transformations. To expand product scope, we are developing biocompatible processes that combine biocatalytic reactions with chemo‐catalysis in single‐flask processes. Here, we show that a chemocatalysed Pictet‐Spengler annulation can be interfaced with biocatalysed alcohol oxidation. This two‐step, one‐pot cascade reaction converts tyramine and aliphatic alcohols to tetrahydroisoquinoline alkaloids in aqueous buffer at mild pH. Tryptamine derivatives are also efficiently converted to tryptolines. Optimization of stoichiometry, pH, reaction time, and whole‐cell catalyst deliver the tetrahydroisouinolines and tryptolines in >90 % and >40 % isolated yield, respectively, with excellent regioselectivity. 

Dinitroalkanes are powerful synthetic building blocks because of the versatility of the 1,3-dinitro motif. Here, we show that dinitroalkanes can be synthesized from aliphatic aldehydes in a three-step cascade reaction catalysed by phosphate buffer and the amino acid lysine. We further show that this methodology can be expanded to limited alcohol substrates (1-butanol and 1-pentanol) with the inclusion of a biocatalysed alcohol oxidation. Simultaneous addition of all reagents gives a maximal yield of 52% of 3-(nitromethyl)hexane, derived from 1-butanol and nitromethane, whereas staggering the introduction of the amino acid catalyst and nitromethane substrate boosts the yield to 71% of 3-(nitromethyl)hexane with near-quantitative consumption of the n-butyraldehyde intermediate. Taken together, this work presents a mild synthetic method that couples multi-step catalytic cascades generate 1,3-dinitroalkanes.