4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• , we report the synthesis of 4-(1-methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones via a reversible transimination reaction between Schiff’ base (C=N) linkage-containing pyrrolidine-2,3-dione derivatives and methylamine with yields of 80 to 92%. In addition to nuclear magnetic resonance

• interactions also contribute to the stabilization of the ligand–iNOS complexes. In particular, 4-(1-methylamino)ethylidene-5-phenyl-1-(3-nitrophenyl)pyrrolidine-2,3-dione (5e) exhibited the strongest binding affinity (−9.51 kcal/mol) and demonstrated significant inhibitory activity against nitric oxide (NO

• ) production, with an IC50 value of 43.69 ± 5.26 µM. The presence of an electron-withdrawing group (-NO2 group) on the benzene ring at the 1-position of the pyrrolidine-2,3-dione subunit in compound 5e may be responsible for the observed high inhibition activity due to the enhancement and optimization of

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was

• . Keywords: 4-acetyl-3-hydroxy-3-pyrroline-2-ones; 1,5-dihydro-2H-pyrrol-2-ones; pyrrolidine-2,3-dione; 2-pyrrolidinone derivative; 3-pyrroline-2-one; Introduction 2-Pyrrolidone, also known as γ-lactam, is a five-membered heterocyclic ring containing four carbon and one nitrogen atoms [1]. This γ-lactam

• -acetyl-3-hydroxy-3-pyrroline-2-ones via multicomponent reactions of ethyl 2,4-dioxovalerate with aromatic aldehydes, and aniline in glacial acetic acid. These 2-pyrrolidinone derivatives were then reacted with aliphatic amines in ethanol to obtain a library of 1,4,5-trisubstituted pyrrolidine-2,3-dione

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• ; pyrrolidine-2,3-dione; Introduction The Michael reaction is a powerful reaction that has been so far applied for the formation of carbon–carbon and carbon–heteroatom bonds in organic synthesis [1][2]. After the renaissance of organocatalysis in the year 2000, this field has been applied tremendously for the

• -dione 1b with a 4-methylbenzylidene-substituent provided the product 3o in 83% yield and 72% ee (Table 3, entry 1). A similar enantioselectivity was obtained with the 4-tert-butylenzylidene-substituted pyrrolidine-2,3-dione 1c (Table 3, entry 2). Then, different 4-halobenzylidene-substituted pyrrolidine

• ) derivatives (Table 3, entries 3–5). These products could be particularly useful for further transformations via cross-coupling reactions. The ortho-fluoroarylidene-substituted pyrrolidine-2,3-dione 1g also participated in the reaction to deliver product 3t in 86% ee (Table 3, entry 6). 2,4-Disubstitution at