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

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(sp 3 )−N bond and a C(sp 2 )−C(sp 2 ) 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 (IC 50 = 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.

Metal-Free Catalyzed Oxidation/Decarboxylative [3+2] Cycloaddition Sequences of 3-Formylchromones to Access Pyrroles with Anti-Cancer Activity

“…Over the past few years, we have been focusing on developing diverse heterocycle synthesis using a 3-formylchromone core [27][28][29]. Chromone, an undoubtedly activated Michael acceptor and a high-value starting material, has been the subject of our interest.…”