Classes of Amides that Undergo Selective N–C Amide Bond Activation: The Emergence of Ground-State Destabilization

Abstract

Ground-state destabilization of the N−C(O) linkage represents a powerful tool to functionalize the historically inert amide bond. This burgeoning reaction manifold relies on the availability of amide bond precursors that participate in weakening of the n N → π* C=O conjugation through N−C twisting, N pyramidalization, and n N electronic delocalization. Since 2015, acyl N−C amide bond activation through ground-state destabilization of the amide bond has been achieved by transition-metal-catalyzed oxidative addition of the N−C(O) bond, generation of acyl radicals, and transition-metal-free acyl addition. This Perspective summarizes contributions of our laboratory in the development of new ground-state-destabilized amide precursors enabled by twist and electronic activation of the amide bond and synthetic utility of ground-state-destabilized amides in cross-coupling reactions and acyl addition reactions. The use of ground-state-destabilized amides as electrophiles enables a plethora of previously unknown transformations of the amide bond, such as acyl coupling, decarbonylative coupling, radical coupling, and transition-metal-free coupling to forge new

Computation-Assisted Design of ssDNA Framework Nanorobots for Cancer Logical Recognition, Toehold Disintegration, Visual Dual-Diagnosis, and Synergistic Therapy

“…As shown in Figure E, a blue-shift of UV–vis absorption between 260 and 280 nm was observed after the loading of phi29 to DNA. This was attributed to the increased transition energy by the destruction of π–π* transition structures via loading of enzymes on ssDNA nanorobots. , In addition, the characteristic peaks of the phi29 polymerase in the circular dichroism (CD) spectrum also confirmed the enzyme modifications (Figure F). Furthermore, both polymerization kinetics and binding constant ( K d ) were evaluated by real-time FL measurements (Figure G) and isothermal titration calorimetry (ITC) (Figure H), respectively.…”

“…Recently, VEGF siRNA and HER2 siRNA were reported to possess synergic effects on cell growth, migration, spreading, attachment and apoptosis, and synergistic silencing on VEGF. , Therefore, these two siRNAs were selected to be loaded on nanorobots for synergistic gene silencing. Guided by the sgc4f and sgc8c aptamer modules, the nanorobots entered the CEM cells under logic dual recognition.…”

“…Recently, VEGF siRNA and HER2 siRNA were reported to possess synergic effects on cell growth, migration, spreading, attachment and apoptosis, and synergistic silencing on VEGF. 21,22 Therefore, these two siRNAs were selected to be Finally, synergistic gene silencing by the present ssDNA nanorobots was evaluated in sorted CEM tumor-bearing nude mice. Different groups of siRNA-loaded carriers were prepared to be delivered for gene silencing treatments.…”

Structure and Additive-free Transamidation of Planar N-Cyano Amides

“…The Journal of Organic Chemistry (100), 180 (11), 178 (7), 137 (11), 136 (90), 122 (14), 121 (60), 109 (10), 106 (26), 77 (11), 43 (11). HRMS (EI) m/z: [M] + Calcd for C 10 H 13 NO 2 179.0941; found 179.0944.…”

The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3–sp2 Carbon–Carbon Bonds

“…We envisioned the amine-acid C(sp 3 )-C(sp 2 ) coupling could be achieved through reductive crosscoupling of carboxylic acids activated as N-acyl-glutarimides [27][28][29][30][31][32] with alkyl amine-derived pyridinium salts. 12,[20][21][22][33][34][35][36][37][38][39][40][41] Using these coupling partners, we embarked on a high-throughput experimentation (HTE) optimization campaign (Figure 2A), utilizing tools for reaction miniaturization in concert with Based on these conditions, we next designed a reaction array using 24 diverse nitrogen ligands (Figure 2B, entry 2).…”