N -Acyl Hemiperaminals: From Bioactive Skeleton Editing of Artemisinin to Programmable Handles for α-Amido Functionalization and Bioactive Peroxides
- 1Xiamen University , , , ,
- 2Chinese Academy of Sciences , , 300 Feng Lin Road , ,
Abstract
Late-stage molecular editing is vital for drug diversification and SAR studies. However, programmable peroxide-based editing handles for amides, α-amino acids, peptide- and drug-relevant scaffolds remain largely unexplored, particularly N-acyl hemiperaminals. Inspired by the molecular editing conception for the bioactive skeleton of artemisinin, we report herein efficient syntheses of structurally diverse N-acyl hemiperaminals via aerobic photocatalytic α-amido C–H oxidative functionalization and oxidative decarboxylative coupling of α-amino acids. Notably, the oxidative decarboxylative of dipeptides and tripeptides facilitates the late-stage modification of peptidomimetic drugs and drug-derived scaffolds. Investigations into the chemical properties of N-acyl hemiperaminals suggest their potential as programmable molecular editing handles for the facile construction of α-amido C–C bonds via Lewis acid-catalyzed nucleophilic substitution and titanocene-catalyzed radical cross-coupling. Importantly, as the derivatives, O-alkylated peroxides exhibit potent antimalarial activity, and 6-amido-1,2,4-trioxanes demonstrate powerful and broad-spectrum anticancer activities. This work will enhance the investigation and application of organic peroxides, advancing novel pharmaceuticals by establishing these peroxides as versatile editing linchpins.
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BibTeX
@article{li2026acyl,
title = {{N -Acyl Hemiperaminals: From Bioactive Skeleton Editing of Artemisinin to Programmable Handles for α-Amido Functionalization and Bioactive Peroxides}},
author = {Yuda Li and Han Gao and Jianliang Ye and Hangtao Zhou and Qian Zhu and Dunpu Rao and Li Li and Lihua Wang and Duanqiu Zuo and Ting Lin and Sibao Wang and Xianming Deng and Xiao Zheng},
journal = {JACS Au},
year = {2026},
month = oct,
doi = {10.1021/jacsau.6c00996},
url = {https://pubs.acs.org/jaaucr/article/6/10/5577/5444890/N-Acyl-Hemiperaminals-From-Bioactive-Skeleton},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - N -Acyl Hemiperaminals: From Bioactive Skeleton Editing of Artemisinin to Programmable Handles for α-Amido Functionalization and Bioactive Peroxides
AU - Yuda Li
AU - Han Gao
AU - Jianliang Ye
AU - Hangtao Zhou
AU - Qian Zhu
AU - Dunpu Rao
AU - Li Li
AU - Lihua Wang
AU - Duanqiu Zuo
AU - Ting Lin
AU - Sibao Wang
AU - Xianming Deng
AU - Xiao Zheng
PY - 2026
DA - 2026/10/05
JO - JACS Au
DO - 10.1021/jacsau.6c00996
UR - https://pubs.acs.org/jaaucr/article/6/10/5577/5444890/N-Acyl-Hemiperaminals-From-Bioactive-Skeleton
AB - Late-stage molecular editing is vital for drug diversification and SAR studies. However, programmable peroxide-based editing handles for amides, α-amino acids, peptide- and drug-relevant scaffolds remain largely unexplored, particularly N-acyl hemiperaminals. Inspired by the molecular editing conception for the bioactive skeleton of artemisinin, we report herein efficient syntheses of structurally diverse N-acyl hemiperaminals via aerobic photocatalytic α-amido C–H oxidative functionalization and oxidative decarboxylative coupling of α-amino acids. Notably, the oxidative decarboxylative of dipeptides and tripeptides facilitates the late-stage modification of peptidomimetic drugs and drug-derived scaffolds. Investigations into the chemical properties of N-acyl hemiperaminals suggest their potential as programmable molecular editing handles for the facile construction of α-amido C–C bonds via Lewis acid-catalyzed nucleophilic substitution and titanocene-catalyzed radical cross-coupling. Importantly, as the derivatives, O-alkylated peroxides exhibit potent antimalarial activity, and 6-amido-1,2,4-trioxanes demonstrate powerful and broad-spectrum anticancer activities. This work will enhance the investigation and application of organic peroxides, advancing novel pharmaceuticals by establishing these peroxides as versatile editing linchpins.
SN - 2691-3704
ER -