459-32-5

Usage

Uses

Used in Pharmaceutical Industry:
4-Fluorocinnamic acid is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique chemical properties allow it to be a key component in the development of new drugs with potential therapeutic applications.
Used in Microbiology:
4-Fluorocinnamic acid is used as a growth medium component for specific bacterial strains, such as Arthrobacter sp. strain G1. This application aids in the study and cultivation of these microorganisms, which can have implications in biotechnology and environmental science.
Used in Environmental Science:
The shock loading of 4-fluorocinnamic acid (4-FCA) is treated using a rotating biological contactor (RBC), which is a method employed in environmental science to manage and treat waste streams containing 4-Fluorocinnamic acid. This application demonstrates its relevance in waste management and pollution control.

InChI:InChI=1/C9H7FO2/c10-8-4-1-7(2-5-8)3-6-9(11)12/h1-6H,(H,11,12)/p-1/b6-3+

Upstream product

• 108-24-7 acetic anhydride 
• 459-57-4 4-fluorobenzaldehyde 
• 20968-47-2 p-(2,2-Dichlorocyclopropyl)fluorobenzene 
• 141-82-2 malonic acid 
• 105-53-3 diethyl malonate 
• 352-34-1 4-fluoro-1-iodobenzene 
• 79-10-7 acrylic acid 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 24393-50-8 ethyl 4-fluorocinnamate 
• 766-98-3 1-ethynyl-4-fluorobenzene 
• 124-38-9 carbon dioxide 
• 2393-18-2 p-aminocinnamic acid 
• 136265-10-6 ethyl 4-fluorocinnamate 
• 1840-01-3 (E)-1-(2-hydroxyphenyl)-3-(4-fluorophenyl)prop-2-en-1-one 

Downstream Products

• 459-31-4 3-(4-fluorophenyl)propanoic acid 
• 139355-84-3 2-<2-(4-fluorophenyl)ethenyl>4H-3,1-benzoxazin-4-one 
• 24393-50-8 ethyl 4-fluorocinnamate 
• 66166-60-7 N-(p-Fluorstyryl)formamid 
• 13565-08-7 4-fluorocinnamoyl chloride 
• 141944-00-5 2,3-dihydro-2-(4-fluorophenyl)-1,5-benzothiazepin-4(5H)-one 
• 100891-10-9 methyl p-fluorocinnamate 
• 315706-75-3 3-(4-fluoro-phenyl)-N-(4-propyl-cyclohexyl)-acrylamide 
• 4926-12-9 4-(4-fluorophenyl)dihydropyran-2,6(3H)-dione 
• 3449-63-6 3-(4-fluorophenyl)pentan-1,5-dioic acid 
• 349446-90-8 2-(4-fluorophenyl)-1,1,3-trimethoxy carbonyl propane 
• 349446-94-2 (4R,1'S)-4-(4-fluorophenyl)-1-(1'-phenylethyl)piperidin-2-one 
• 349446-96-4 {(3S,4R)-4-(p-fluorophenyl)-3-(hydroxymethyl)-1-[1-(S)-phenylethyl]}piperidine 
• 349446-92-0 (3R)-3-(4-fluorophenyl)-5-hydroxypentanoic acid (1S)-1-phenylethylamide 

Relevant academic research and scientific papers

Quorum sensing and nf-κb inhibition of synthetic coumaperine derivatives from piper nigrum

Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.

Photocatalytic Oxidative [2+2] Cycloelimination Reactions with Flavinium Salts: Mechanistic Study and Influence of the Catalyst Structure

Flavinium salts are frequently used in organocatalysis but their application in photoredox catalysis has not been systematically investigated to date. We synthesized a series of 5-ethyl-1,3-dimethylalloxazinium salts with different substituents in the positions 7 and 8 and investigated their application in light-dependent oxidative cycloelimination of cyclobutanes. Detailed mechanistic investigations with a coumarin dimer as a model substrate reveal that the reaction preferentially occurs via the triplet-born radical pair after electron transfer from the substrate to the triplet state of an alloxazinium salt. The very photostable 7,8-dimethoxy derivative is a superior catalyst with a sufficiently high oxidation power (E=2.26 V) allowing the conversion of various cyclobutanes (with Eox up to 2.05 V) in high yields. Even compounds such as all-trans dimethyl 3,4-bis(4-methoxyphenyl)cyclobutane-1,2-dicarboxylate can be converted, whose opening requires a high activation energy due to a missing pre-activation caused by bulky adjacent substituents in cis-position.

Iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabled aldehyde C-H methylation

A practical and general iron-catalyzed domino decarboxylation-oxidation of α,β-unsaturated carboxylic acids enabling aldehyde C-H methylation for the synthesis of methyl ketones has been developed. This mild, operationally simple method uses ambient air as the sole oxidant and tolerates sensitive functional groups for the late-stage functionalization of complex natural-product-derived and polyfunctionalized molecules.

Piperlongumine analogs promote A549 cell apoptosis through enhancing ROS generation

Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electronwithdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.

Larvicidal activity and in silico studies of cinnamic acid derivatives against Aedes aegypti (Diptera: Culicidae)

Cinnamic acid derivatives (CAD's) represent a great alternative in the search for insecticides against Aedes aegypti mosquitoes since they have antimicrobial and insecticide properties. Ae. aegypti is responsible for transmitting Dengue, Chikungunya, and Zika viruses, among other arboviruses associated with morbimortality, especially in developing countries. In view of this, in vitro analyses of n-substituted cinnamic acids and esters were performed upon 4th instar larvae (L4) of Ae. aegypti, as well as, molecular docking studies to propose a potential biological target towards this mosquitoes species. The larvicide assays proved that n-substituted ethyl cinnamates showed a more pronounced activity than their corresponding acids, in which p-chlorocinnamate (3j) presented a LC50 value of 8.3 μg/mL. Thusly, external morphologic alterations (rigid and elongated body, curved bowel, and translucent or darkened anal papillae) of mosquitoes’ group exposed to compound 3j, were observed by microscopy. In addition, an analytical method was developed for the quantification of the most promising analog by using high-performance liquid chromatography with UV detection (HPLC-UV). Molecular docking studies suggested that the larvicide action is associated with inhibition of acetylcholinesterase (AChE) enzyme. Therefore, expanding the larvicidal study with the cinnamic acid derivatives against the vector Ae. aegypti is important for finding search for more effective larvicides and with lower toxicity, since they have already shown good larvicidal properties against Ae. aegypti.

Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia

Recently, irreversible inhibitors have attracted great interest in antitumors due to their advantages of forming covalent bonds to target proteins. Herein, some benzothiazepinone compounds (BTZs) have been designed and synthesized as novel covalent GSK-3β inhibitors with high selectivity for the kinase panel. The irreversible covalent binding mode was identified by kinetics and mass spectrometry, and the main labeled residue was confirmed to be the unique Cys14 that exists only in GSK-3β. The candidate 4-3 (IC50 = 6.6 μM) showed good proliferation inhibition and apoptosis-inducing ability to leukemia cell lines, low cytotoxicity on normal cell lines, and no hERG inhibition, which hinted the potential efficacy and safety. Furthermore, 4-3 exhibited decent pharmacokinetic properties in vivo and remarkably inhibited tumor growth in the acute promyelocytic leukemia (APL) mouse model. All the results suggest that these newly irreversible BTZ compounds might be useful in the treatment of cancer such as APL.

Synthesis method of selenium-containing isochroman compound

The invention discloses a synthesis method of a selenium-containing isochroman compound. The synthesis method comprises the following steps: under the protection of nitrogen, adding N-phenylseleno saccharin (NPSSac) into a reactor, then adding dichloromethane to completely dissolve the N-phenylseleno saccharin, adding a 1-[(cinnamoxy) methyl]-3, 4, 5-trimethoxy benzene compound and boron trifluoride diethyl etherate after the N-phenylseleno saccharin is completely dissolved, stirring at 20-60 DEG C for 2-6 hours until the reaction is complete, and after the reaction is finished, quenching, extracting, combining organic phases, drying, concentrating, separating and purifying to obtain the selenium-containing isochroman compound. The synthesis method disclosed by the invention is relatively easy to operate, mild in reaction condition, relatively high in yield, environment-friendly and suitable for large-scale industrial production.

Photo-Promoted Decarboxylative Alkylation of α, β-Unsaturated Carboxylic Acids with ICH2CN for the Synthesis of β, γ-Unsaturated Nitriles

An efficient, catalyst/photocatalyst-free, and cost-effective methodology for the decarboxylative alkylation of α,β-unsaturated carboxylic acids to synthesize β,γ-unsaturated nitriles has been developed. The reaction proceeded in an environmentally benign atmosphere of blue light-emitting diode irradiation with K2CO3 and water at room temperature. The methodology worked for a wide range of substrates (22 examples) with up to 83% yield. The protocol is also compatible for gram-scale synthesis.

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.

Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives

This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.