Entry to 4,5-fused coumarin frameworks radical-promoted alkylative intramolecular C5-annulation.

An unprecedented radical-promoted strategy involving a domino alkylation/intramolecular C5-annulation of -acryloyl-4-amino coumarin has been devised for the assembly of 4,5-fused coumarin scaffolds. This protocol employs silver-catalyzed oxidative decarboxylation for the generation of alkyl radicals from carboxylic acids, which were used as radical precursors. This method has also been extended to a diverse range of carbon-centered radicals generated from 2-oxo acids, a 1,3-dicarbonyl compound, isopropanol and acetone.

Comprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing Factor in Leukemia Cells.

Mutations in RNA splicing factor genes including , , and have been reported to contribute to development of myeloid neoplasms including myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML). Chemical tools targeting cells carrying these mutant genes remain limited and underdeveloped. Among the four proteins, mutant U2AF1 (U2AF1) acquires an altered 3' splice site selection preference and co-operates with the wild-type U2AF1 (U2AF1) to change various gene isoform patterns to support MDS cells survival and proliferation.

-Cyclization of unactivated biaryl ynones leading to thio-functionalized spirocyclic enones.

Ceric ammonium nitrate (CAN)-promoted oxidative -cyclization of unactivated biaryl ynones with -centered radicals (SCN/SCF) to access spiro[5,5]trienones has been established. This approach displayed excellent regioselectivity towards spirocyclization and tolerated a variety of functional groups. Dearomatization of hitherto unknown aryl/heteroaryl groups is also disclosed.

Tandem 1,6-Addition/Annulations of Alkynyl -Quinone Methides with Bis-nucleophiles: Entry to Functionalized Furans, Isoxazoles, Pyrazoles, and Pyridines.

The reaction of alkynyl -quinone methide (QM) with keto-methylenes through a base-mediated tandem 1,6-addition/annulation sequence, [2 + 3] annulation, affording the furans is reported for the first time. A variety of functionalized furans, including fused derivatives, were obtained in good to excellent yields under mild reaction conditions. The efficacy of alkynyl QMs is highlighted by extending their use to access isoxazoles, pyrazoles [3 + 2] annulation, and pyridines through [3 + 3] annulation in the presence of different bis-nucleophiles.

Domino alkyne insertion/aldol reaction/aromatization of 2-alkynyl indole-3-carbaldehyde with 1,3-diketones: entry to 2-indolyl phenols.

A novel one-pot base-promoted insertion of indolyl 2-alkynes into a C-C single bond of 1,3-diketones, followed by intramolecular aldol reaction and dehydrative aromatization is described. This reaction cascade leads to the construction of 2-indolyl phenols involving the formation of the C1-C2 and C3-C4 bonds of phenols resulting from the formal insertion process with a good substrate scope. Further, these bifunctional compounds were used in a novel arylative annulation in the presence of Grignard reagents to provide chromeno-indole frameworks.

FeCl-mediated selenylative benzannulation of aryl alkynones to 3-selenyl β-naphthols.

An efficient selenylative cyclization of aryl-alkynones with diselenides in the presence of iron(III)chloride at room temperature to prepare 3-seleno-2-naphthols in good yields has been described. Furthermore, the resulting products were transformed into selenyl-naphthofuran and selenyl-1,2-naphthoquinone derivatives.

Total synthesis of remdesivir.

Remdesivir, the first drug approved by the FDA to treat COVID-19, is in high demand for patients infected with the SARS-CoV-2 virus. Herein, we report a facile approach minimizing the protecting group manipulations to afford remdesivir in good overall yield.

Iodo- and Chalcogenoannulation of Morita-Baylis-Hillman Alcohols of Propiolaldehydes: Entry to Functionalized 2-Pyrones.

An efficient intramolecular annulation of Morita-Baylis-Hillman (MBH) alcohols of propiolaldehydes is developed in the presence of ICl or PhSeSePh/PhSSPh-CuCl. This cyclization offers access to a wide variety of iodinated or chalcogenated 3-(chloromethyl)-2-pyrones in good yields. The chloromethyl group of the obtained 2-pyrones has been easily converted to introduce other handy functionalities, which allowed for further transformations to synthesize diverse 2-pyrone containing molecules.

Oxa-[3+3] annulation of MBH-carbonates of propiolaldehydes with α-nitro/bromo ketones to access 2H-pyrans.

A novel alkyne-assisted annulation reaction of MBH-carbonates of propiolaldehydes with α-nitro/bromo ketones is reported, providing a facile synthesis of substituted 2H-pyrans in good yields. This reaction divulges the inimitable reactivity of the MBH-carbonates of propiolaldehydes as C3-synthons wherein the alkyne functionality promoted the reaction without participating in the oxa-[3+3] annulation. The obtained products, having alkyne and ester functionalities, allowed further annulations to generate diverse pyrano[3,4-c]pyran-1-ones.