141236-49-9

Upstream product

• 616-45-5 2-pyrrolidinon 
• 109-72-8 n-butyllithium 
• 656821-45-3 3-phenyl acrylic acid pentafluorophenyl ester 
• 102-92-1 Cinnamoyl chloride 
• 14371-10-9 (E)-3-phenylpropenal 
• 100-52-7 benzaldehyde 
• 104-55-2 3-phenyl-propenal 
• 621-82-9 Cinnamic acid 
• 140-10-3 (E)-3-phenylacrylic acid 

Downstream Products

• 308277-23-8 (S)-N-benzyl-β³-homophenylglycine 
• 16460-78-9 (S)-3-phenylvaleric acid 
• 905994-81-2 (3S)-1-(3-phenylpentanoyl)pyrrolidin-2-one 

Relevant academic research and scientific papers

Meta-substituted piperlongumine derivatives attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis

Piperlongumine (PL) has been showed to have multiple pharmacological activities. In this study, we reported the synthesis of three series of PL derivatives, and evaluation of their anti-inflammatory effects in both lipopolysaccharide (LPS)-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. Our results presented that two meta-substituent containing derivatives 1–3 and 1–6, in which γ-butyrolactam replaced α,β-unsaturated δ-valerolactam ring of PL, displayed low cytotoxicity and effective anti-inflammatory activity. Molecular docking also showed that the meta-substituted derivative, compared with the corresponding ortho- or para-substituted derivative, had significant interactions with the amino acid residues of CD14, which was the core receptors recognizing LPS. In vitro and in vivo studies, 1–3 and 1–6 could inhibit the expression of pro-inflammatory cytokines, and the excessive production of reactive nitrogen species and reactive oxygen species. Oral administration of 100 mg/kg/day of 1–3 or 1–6 alleviated the severity of clinical symptoms of colitis in mice, and significantly reduced the colonic tissue damage to protect the colonic tissue from the DSS-induced colitis. These results suggested that meta-substituted derivatives 1–3 and 1–6 were potential anti-inflammatory agents, which may lead to future pharmaceutical development.

Synthesis, characterization, and molecular docking studies of N-acylated butyro and valerolactam derivatives with antiproliferative and cytotoxic activities

Background: Electrophilic compounds bearing Michael acceptors present great promise in anticancer drug discovery. Methods: Drawing inspirations from cytotoxic Piper lactam alkaloids, twelve N-acylated butyro- and valerolactams were prepared and evaluated

N-Acylation of Oxazolidinones via Aerobic Oxidative NHC Catalysis

The first N-acylation of synthetically useful oxazolidinones with aldehydes using aerobic oxidative NHC catalysis is reported. The reaction offers a broad scope of functionalized oxazolidinones in good to excellent yields. Careful choice of electron transfer mediators proved pivotal to achieve efficient aerobic N-acylation, which has previously proven difficult using NHC catalysis. The methodology allows a mild entry to acylated oxazolidinones, avoiding the use of hazardous and reactive prefunctionalized substrates.

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.

Direct N-acylation of lactams, oxazolidinones, and imidazolidinones with aldehydes by Shvo's catalyst

Direct N-acylation of lactams, oxazolidinones, and imidazolidinones was achieved with aldehydes by Shvo's catalyst without using any other stoichiometric reagent. The N-acylations with α,β-unsaturated aldehydes were achieved with excellent yields.

Highly enantioselective copper-phosphoramidite-catalyzed conjugate addition of dialkylzinc reagents to acyclic α,β-unsaturated imides

A new and practical way to introduce an alkyl fragment in the β-position of aliphatic carboxylic acid derivatives with high enantioselectivities by the use of a commercially available chiral ligand is reported. N-Acylpyrrolidinones, as simple derivatives

Rational Design of Highly Diastereoselective, Organic Base-Catalyzed, Room-Temperature Michael Addition Reactions

Via the rational design of a single-preferred transition state, stabilized by electron donor - acceptor-type attractive interactions, structural and geometric requirements for the corresponding starting compounds have been determined. The Ni(II) complex of the Schiff base of glycine with o-[N-α-picolylamino]acetophenone, as a nucleophilic glycine equivalent, and N-(trans-enoyl)oxazolidin-2-ones, as derivatives of an α,β-unsaturated carboxylic acid, were found to be the substrates of choice featuring geometric/conformational homogeneity and high reactivity. The corresponding Michael addition reactions were found to proceed at room temperature in the presence of catalytic amounts of DBU to afford quantitatively the addition products with virtually complete diastereoselectivity. Acidic decomposition of the products followed by treatment of the reaction mixture with NH4OH gave rise to the diastereomerically pure 3-substituted pyroglutamic acids.

N-benzylhydroxylamine addition to β-aryl enoates. Enantioselective synthesis of β-aryl-β-amino acid precursors

(matrix presented) Chiral Lewis acid catalyzed N-benzylhydroxylamine addition to pyrrolidinone-derived enoates afforded β-aryl-β-amino acid derivatives in high enantiomeric purity with moderate to very good chemical efficiency.

Synthesis of mixed acyclic imides using pentafluorophenyl esters

Mixed acyclic imides are assembled using amide anions and pentafluorophenyl esters reacted in THF at low temperature. Sodium hexamethyldisilazide deprotonates lactam 4 followed by addition of pentafluorophenyl (PFP) esters to give imides in high yield (85