2. Academic Validation
  3. Unexpected Cascade Sequence Forming the C(sp3)-N/C(sp2)-C(sp2) Bond: Direct Access to γ-Lactam-Fused Pyridones with Anticancer Activity

Unexpected Cascade Sequence Forming the C(sp3)-N/C(sp2)-C(sp2) Bond: Direct Access to γ-Lactam-Fused Pyridones with Anticancer Activity

  • J Org Chem. 2023 Jul 7;88(13):7998-8009. doi: 10.1021/acs.joc.3c00031.
Ya-Nan An 1 2,  Jiu-Hong Huang 1,  Shi-Fang Xu 1,  Xiao-Lin Wang 1,  Cheng-He Zhou 2,  Zhi-Gang Xu 1,  Jie Lei 1,  Zhong-Zhu Chen 1
Affiliations

Affiliations

  • 1 College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, 319 Honghe Ave., Yongchuan, Chongqing 402160, China.
  • 2 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China.
PMID: 37279456 DOI: 10.1021/acs.joc.3c00031
Abstract

An unexpected Ugi cascade reaction was developed for the facile construction of γ-lactam-fused pyridone derivatives with high tolerance of substrates. A C(sp3)-N bond and a C(sp2)-C(sp2) bond were formed together, accompanied by a chromone ring-opening in Ugi adducts, under the basic conditions without any metal catalyst for the whole process. Screening data of several difficult-to-inhibit Cancer cell lines demonstrated that 7l displayed a high cytotoxicity against HCT116 cells (IC50 = 5.59 ± 0.78 μM). Taken together, our findings revealed new insights into the molecular mechanisms underlying compound 7l and provided potential usage of this scaffold for Cancer therapeutics.

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