Rh-Catalyzed C-H Activation/Annulation of Enaminones and Cyclic 1,3-Dicarbonyl Compounds: An Access to Isocoumarins.

A facile access to isocoumarins has been established via rhodium(III)-catalyzed C-H bond activation and intramolecular C-C cascade annulation of enaminones and cyclic 1,3-dicarbonyl compounds. The synthetic protocol features a wide range of substrates with high functional group tolerance, mild reaction conditions, and the selective cleavage of the enaminone C-C bond. Notably, the cyclic 1,3-dicarbonyl compounds can in situ-generate iodonium ylide as a carbene precursor to prepare polycyclic scaffolds by reacting with PhI(OAc)2. The application of this method to prepare useful synthetic precursors and bioactive skeletons is also exemplified.

Sulfoximines Assisted Rh(III)-Catalyzed C-H Activation/Annulation Cascade to Synthesize Highly Fused Indeno-1,2-benzothiazines.

A facile access to highly fused tetracyclic indeno-1,2-benzothiazines has been established via a Rh(III)-catalyzed C-H bond activation and intramolecular annulation cascade between sulfoximides and all-carbon diazo indandiones. This strategy is characterized by the fact that the diazo coupling partners do not require preactivation, along with its high efficiency, broad substrate generality, and facile transformation. Particularly, the highly conjugated tetracyclic products demonstrate good optical properties and can easily enter cells to emit bright fluorescence for live cell imaging.

Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms.

Macrocycles often exhibit good biological properties and potential druggability, which lead to versatile applications in the pharmaceutical industry. Herein, we report a highly efficient and practical methodology for the functionalization and macrocyclization of Trp and Trp-containing peptides via Pd(II)-catalyzed C-H alkenylation at the Trp C4 position. This method provides direct access to C4 maleimide-decorated Trp-containing peptidomimetics and maleimide-braced 17- to 30-membered peptide macrocycles. In particular, these unique macrocycles revealed low micro- to sub-micromolar EC50 values with promising anti-SARS-CoV-2 activities. Further explorations with computational methodologies and experimental validations indicated that these macrocycles exert antiviral effects through binding with the N protein of SARS-CoV-2.