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Updated: Jan 6, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Introduction of the α-ketoamide structure: en route to develop hydrogen peroxide responsive prodrugs
Tingting Meng1,2, Jing Han3, Pengfei Zhang1
1Key Laboratory of Carbohydrate Chemistry and Biotechnology , Ministry of Education , School of Biotechnology , Jiangnan University , Wuxi 214122 , P. R. China . Email: jfu@jiangnan.edu.cn ;
Abstract:
Leveraging the elevated levels of hydrogen peroxide (H2O2) in cancer, inflammatory diseases and cardiovascular disorders, H2O2-activated promoieties have been widely used in drugs and biomaterials design. However, the overwhelming majority of the promoieties only share the common structure of a H2O2-responsive arylboronic acid/ester moiety with low diversity. We report here an unprecedented strategy to construct novel H2O2-responsive prodrugs based on an α-ketoamide structure. As a proof of concept, we designed and synthesized a panel of α-ketoamide based nitrogen mustard prodrugs, among which KAM-2 showed potent growth inhibitory activity and high selectivity toward cancer cells. The H2O2-trigged decomposition of KAM-2 was validated, and the DNA damaging and apoptosis promoting activity attributed to the released nitrogen mustard were demonstrated. Our work unveils α-ketoamide as a new scaffold for prodrug design and may quickly inspire future developments.
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