Visible-light promoted oxidative annulation of 2-naphthols with phenylglyoxal monohydrates toward hydroxy-naphthofuranone and its derivatives.

A highly efficient and innovative method involving base-mediated oxidative annulation between 2-naphthols and phenylglyoxal monohydrate under visible light irradiation has been successfully developed. This method leads to the formation of oxygen-containing heterocyclic compounds, particularly hydroxy-naphthofuranone derivatives, encompassing a unique quaternary carbon center. An X-ray diffraction study has unambiguously confirmed the structure of one such derivative. In particular, water molecules in this reaction serve various functions as a solvent, reagent, and additive, with the conversion of the process found to be influenced by the volume of water present. This atom-economical approach demonstrates tolerance for different substituents in both phenylglyoxal monohydrate and 2-naphthol, enabling the synthesis of a variety of naphthofuranones in satisfactory to good yields. The formation of a naphthofuranium cationic intermediate under acidic circumstances enables the formation of C-C or C-O bonds with a wide range of aromatic or alcoholic nucleophilic partners. Furthermore, the identification and generation of pinacol-type starting precursors from these naphthofuranone derivatives enable the synthesis of highly regioselective naphthofuran derivatives.

An efficient method to access spiro pseudoindoxyl ketones: evaluation of indoxyl and their N-benzylated derivatives for inhibition of the activity of monoamine oxidases.

A simple, metal-free approach was developed to obtain novel pseudoindoxyl derivatives. The reaction was mediated by tBuOK on tetrahydrocarbazole 8 in dimethyl sulfoxide (DMSO) at room temperature through the hydroxylation of the indole double bond and a subsequent pinacol-type rearrangement. Spiro pseudoindoxyl compounds and their N-benzylated derivatives were assessed for their inhibitory activities against monoamine oxidase (MAO) enzymes. Based on half-maximal inhibitory concentration (IC50) values, 13 compounds were found to have higher inhibitory activity against MAO-B than against MAO-A. With regard to MAO-B inhibition, 11f showed the best inhibitory activity, with an IC50 value of 1.44 µM, followed by 11h (IC50 = 1.60 µM), 11j (IC50 = 2.78 µM), 11d (IC50 = 2.81 µM), and 11i (IC50 = 3.02 µM). Compound 11f was a competitive inhibitor with a Ki value of 0.51 ± 0.023 µM. In a reversibility experiment using dialysis, 11f showed effective recovery of MAO-B inhibition similar to that of safinamide. These experiments suggested that 11f was a potent, reversible, and competitive inhibitor of MAO-B activity.

Transition-Metal-Free Dehydrogenation of Benzyl Alcohol for C-C and C-N Bond Formation for the Synthesis of Pyrazolo[3,4-b]pyridine and Pyrazoline Derivatives.

A series of cascade reactions that produce a range of functionalized aromatic heterocyclic compounds with pyrazole/pyrazoline cores have been developed. The method relies on a metal-free dehydrogenative process to produce in-situ benzaldehydes. The produced benzaldehyde was then allowed to react with some other substances, including acetophenone, pyrazole amine, and phenylhydrazine. The intermediate produced from these substrates underwent several chemical processes, including electrocyclization, the aza-Diels-Alder reaction, and the formation of intramolecular C-N bonds. These positive outcomes would open up the possibility of producing biologically active pyrazolo[3,4-b]pyridine and pyrazoline derivatives through a variety of possible reactions.

Dimethyl Sulfoxide-Assisted, Iodine- and Ascorbic Acid-Catalyzed One-Pot Synthetic Approach for Constructing Highly Substituted Pyrazolo[1,5-a]quinoline Thioether Derivatives.

A dimethyl sulfoxide-assisted and iodine/ascorbic acid-catalyzed simple approach to pyrazolo[1,5-a]quinoline thioether derivatives 22 is described. The compounds were identified using 1H NMR, 13C NMR, high-resolution mass spectrometry, and single-crystal X-ray diffractometry. The pyrazolo[1,5-a]quinoline thioether was synthesized in a stepwise fashion through aryl sulfenylation and benzannulation strategies. The generated heteroaryl thioether compounds 23 were exposed to the benzannulation path to produce pyrazolo[1,5-a]quinoline thioether 22. The benzannulation reaction proceeds by way of diazotization of the pyrazole amine derivative 23, radical generation by the removal of nitrogen, and eventually trapping of the aryl radical with the support of phenylacetylene 19. A catalytic amount of ascorbic acid aided the benzannulation reaction. There were several other control studies conducted, including trapping reactions with isopropenyl acetate, tetramethylpiperidine N-oxyl reactions, and reactions without phenylacetylene. Since a change in the substitution has previously demonstrated substantial bioactivity, the core structure of pyrazole was evaluated for functional group tolerance. A reasonable mechanism is then proposed, accompanied by the support of control experiments and scope. A Suzuki reaction was used to create an aryl/heteroaryl compound 35 from one of the synthesized compounds 22b. In the controlled oxidation reaction paths, molecule 22a was selectively transformed into the corresponding sulfoxide 32 and sulfone 33.