Divergent Annulative C–C Coupling of Indoles Initiated by Manganese-Catalyzed C–H Activation

Manganese­(I)-catalyzed C–H activation of indoles and divergent annulative coupling with alkyne-tethered cyclohexadienones has been realized under operationally simple conditions. These annulation systems are under condition control. The coupling in the presence of BPh3 additive followed a C–H activation-alkyne insertion-Michael addition pathway, affording an exocyclic olefin attached to a tetrahydrofuran ring. In contrast, when Zn­(OAc)2/PivOH additives were introduced, initial olefination en route to intramolecular Diels–Alder reaction and subsequent elimination of an alcohol was followed to deliver a fused six-membered ring. The selectivity stands in contrast to those reported using rhodium­(III) and cobalt­(III) catalysts, highlighting the unique reactivity and selectivity of manganese catalysts

Construction of (Dihydro)naphtho[1,8-<i>bc</i>]pyrans via Rh(III)-Catalyzed Twofold C–H Activation of Benzoylacetonitriles

Rh­(III)-catalyzed cascade C–H activation of benzoylacetonitriles and annulation with sulfoxonium ylides was realized, leading to selective synthesis of naphthols, 2,3-dihydronaphtho­[1,8-<i>bc</i>]­pyrans, and naphtho­[1,8-<i>bc</i>]­pyrans. This step-economic reaction proceeded efficiently under mild and redox-neutral conditions via multiple C–H activations

A Stereodivergent–Convergent Chiral Induction Mode in Atroposelective Access to Biaryls via Rhodium-Catalyzed C–H Bond Activation

Understanding the reaction mechanisms, particularly the chiral induction mode, is critical for the development of new asymmetric catalytic reactions. Rhodium­(III)-catalyzed C–H activation en route to atroposelective [4 + 2] annulative coupling with α-diazo β-ketoesters has been realized, affording axially chiral phenanthrenes in good to excellent enantioselectivity. A combination of experimental and computational studies revealed a nontraditional stereodivergent–convergent chiral induction mode. The reaction proceeded with a rhodafluorene intermediate, followed by competitive, constructive, and stereodivergent migratory insertions of the two Rh–C­(aryl) bonds into the carbene species to give β-ketoester intermediates. Then, the other Rh–C­(aryl) bond migratorily inserts into the ketone carbonyl group. Following this stereodetermining carbonyl insertion, an ester-chelated rhodium­(III) alkoxide species bearing two poorly controlled chiral centers and a well-controlled C­(sp2)–C­(sp3) chiral axis is generated. The final product is delivered via stereoconvergent elimination of a rhodium­(III) species with retention of the well-controlled axial chirality and with loss of the central chirality

Azomycin Orchestrate Colistin-Resistant Enterobacter cloacae Complex’s Colistin Resistance Reversal In Vitro and In Vivo

The Enterobacter cloacae complex (ECC) is a group of nosocomial pathogens that pose a challenge in clinical treatment due to its intrinsic resistance and the ability to rapidly acquire resistance. Colistin was reconsidered as a last-resort antibiotic for combating multidrug-resistant ECC. However, the persistent emergence of colistin-resistant (COL-R) pathogens impedes its clinical efficacy, and novel treatment options are urgently needed. We propose that azomycin, in combination with colistin, restores the susceptibility of COL-R ECC to colistin in vivo and in vitro. Results from the checkerboard susceptibility, time-killing, and live/dead bacterial cell viability tests showed strong synergistic antibacterial activity in vitro. Animal infection models suggested that azomycin–colistin enhanced the survival rate of infected Galleria mellonella and reduced the bacterial load in the thighs of infected mice, highlighting its superior in vivo synergistic antibacterial activity. Crystal violet staining and scanning electron microscopy unveiled the in vitro synergistic antibiofilm effects of azomycin–colistin. The safety of azomycin and azomycin–colistin at experimental concentrations was confirmed through cytotoxicity tests and an erythrocyte hemolysis test. Azomycin–colistin stimulated the production of reactive oxygen species in COL-R ECC and inhibited the PhoPQ two-component system to combat bacterial growth. Thus, azomycin is feasible as a colistin adjuvant against COL-R ECC infection