Deoxytrifluoromethylation/aromatization of cyclohexan(en)ones to access highly substituted trifluoromethyl arenes.

Trifluoromethyl arenes (Ar-CF) are amongst the commonly encountered fluorinated substructures in pharmaceutical, agrochemical, and material sciences. However, predominant methods to access Ar-CF possess several limitations, including harsh conditions, lack of availability of substrates, and poor regioselectivity, which combined restrict access to desirable highly functionalized Ar-CF-containing compounds. To expand the scope of accessible Ar-CF-based molecules, we present an orthogonal deoxyfluoroalkylation/aromatization approach that exploits readily accessible and programable cyclohexan(en)one substrates, which undergo a reliable 1,2-addition reaction with the Ruppert-Prakash reagent (TMSCF) followed by aromatization to deliver highly functionalized Ar-CF compounds in a one/two-pot sequence.

N4-Substituted Piperazinyl Norfloxacin Derivatives with Broad-Spectrum Activity and Multiple Mechanisms on Gyrase, Topoisomerase IV, and Bacterial Cell Wall Synthesis.

Fluoroquinolones are an important class of antibiotics with broad-spectrum antibacterial and antitubercular activity. Here, we describe the design and synthesis of a series of 38 4-substituted piperazinyl norfloxacin derivatives. Their activity and mechanism of action were characterized using , , and approaches.

Rational design, synthesis, molecular modeling, biological activity, and mechanism of action of polypharmacological norfloxacin hydroxamic acid derivatives.

Fluoroquinolones are broad-spectrum antibiotics that target gyrase and topoisomerase IV, involved in DNA compaction and segregation. We synthesized 28 novel norfloxacin hydroxamic acid derivatives with additional metal-chelating and hydrophobic pharmacophores, designed to enable interactions with additional drug targets. Several compounds showed equal or better activity than norfloxacin against Gram-positive, Gram-negative, and mycobacteria, with MICs as low as 0.

A diselenide additive enables photocatalytic hydroalkoxylation of -difluoroalkenes.

A photocatalytic hydroalkoxylation reaction enables the coupling of aliphatic alcohols with -difluoroalkenes, expanding the scope of accessible α,α-difluorinated ethers, a desirable substructure for medicinal and agricultural chemists. This reaction exploits an uncommon diselenide co-catalyst to facilitate the net hydrofunctionalization process, which contrasts alternate single-electron reactions that deliver dioxidation products. Future use of this co-catalyst might enable other currently unknown photocatalytic reactions.

General Co-catalytic Hydrothiolation of -Difluoroalkenes.

Regioselective functionalization of -difluoroalkenes enables convergent late-stage access to fluorinated functional groups, though most functionalization reactions proceed through defluorinative functionalization processes that deliver mono-fluorovinyl products. In contrast, fewer reactions undergo net hydrofunctionalization to generate difluorinated products. Herein, we report a photocatalytic hydrothiolation of -difluoroalkenes that enables access to a broad spectrum of α,α-difluoroalkylthioethers.

Design, Synthesis, Molecular Modeling, and Anticancer Evaluation of New VEGFR-2 Inhibitors Based on the Indolin-2-One Scaffold.

A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity.

Enantioselective Total Synthesis of (+)-Sieboldine A.

The first total synthesis of (+)-sieboldine A was completed starting from 5-(p-methoxybenzyloxy)pentyne in 19 steps. The enantioselective Keck allylation provided the dienyne derivative, which was exposed to the Pauson-Khand conditions to afford the bicyclo[4.3.

Synthesis, biological investigation and molecular docking study of N-malonyl-1,2-dihydroisoquinoline derivatives as brain specific and shelf-stable MAO inhibitors.

A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines (9a-b), as monoamine oxidase inhibitors (MAOIs), and β-phenethylamine (14), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) (13a-b and 18). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline.