A research team led by Professor Shen Yangyang and Researcher Gu Yiting from the Frontier Institute of Science and Technology at Xi'an Jiaotong University (XJTU) recently made a breakthrough in the field of carbon radical catalysis.

The team developed a novel carbon radical catalytic system based on the reversible homolytic cleavage of dynamic covalent C(sp³)—C(sp³) bonds. This system enables the efficient and modular synthesis of cis-cyclopentanes under air- and water-compatible conditions, offering a brand-new chemical platform for drug lead discovery.

The findings, titled Bioinspired Carbon Radical Catalysis, were published in the Journal of the American Chemical Society, a flagship journal in the international chemical field.

The method features a broad substrate scope, tolerating a rich variety of functional groups such as sulfones, ketones, imides, phenols, alcohols, epoxides, free amines, alkenes, pyridines, indoles, indazoles, and pyrimidines.

Notably, the approach allows for the highly efficient synthesis of a series of novel cyclic amino acid derivatives. It has also been applied to late-stage modification of natural products (e.g., alantolactone, dehydrocostus lactone, parthenolide) and derivatives of the FDA-approved anticancer drug Ibrutinib.

Gram-scale experiments confirmed the reaction's excellent scalability. The resulting products can be further transformed into complex scaffolds, including spirooxetanes, pyrimidinetriones, polysubstituted naphthalenes, and oxabicyclic amino acids. Furthermore, through photocatalysis, the team achieved 1,4-pyridine migration and the Paternò-Büchi reaction, rapidly unlocking C(sp³)-rich chemical space for lead compound discovery.