96249-87-5

Upstream product

• 120-57-0 piperonal 
• 79-37-8 oxalyl dichloride 
• 2373-80-0 3,4-methylenedioxy-trans-cinnamic acid 
• 2373-80-0 3,4-(methylenedioxy)cinnamic acid 
• 139-85-5 3,4-dihydroxybenzaldehyde 

Downstream Products

• 120680-81-1 2-((E)-3-Benzo[1,3]dioxol-5-yl-acryloylamino)-3-phenyl-propionic acid 
• 114133-04-9 1-(benzoyloxy)-5-<((E)-piperonylacryloyl)oxy>-1(E),3(E)-pentadiene 
• 124778-00-3 (E)-3-(benzo[d][1,3]dioxol-5-yl)-N,N-dimethylacrylamide 
• 159052-13-8 α-(3,4-methylenedioxycinnamoyl)benzylidene(triphenyl)phosphorane 
• 82857-82-7 (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(piperidin-1-yl)prop-2-en-1-one 
• 356546-38-8 N-[(E)-3,4-methylenedioxycinnamoyl]dopamine 
• 125187-31-7 (E)-3-(benzo[d][1,3]dioxol-5-yl)-N-(3,4-dimethoxyphenethyl)acrylamide 
• 31983-44-5 (E)-6-[2-(benzo[1,3]dioxol-5-yl)vinyl]pyran-2-one 
• 1027046-05-4 3-benzo[1,3]dioxol-5-yl-N-(2-bromo-4-fluoro-phenyl)-acrylamide 

Relevant academic research and scientific papers

Design, synthesis, and taste evaluation of a high-intensity umami-imparting oxazole-based compound

Umami taste is imparted predominantly by monosodium glutamate (MSG) and 5′-ribonucleotides. Recently, several different classes of hydrophobic umami-imparting compounds, the structures of which are quite different from MSG, have been reported. To obtain a novel umami-imparting compound, N-cinnamoyl phenethylamine was chosen as the lead compound, and a rational structure-optimization study was conducted on the basis of the pharmacophore model of previously reported compounds. The extremely potent umami-imparting compound 2-[[[2-[(1E)-2-(1,3-benzodioxol-5-yl)ethenyl]-4-oxazolyle]methoxy]methyl]pyridine, which exhibits 27,000 times the umami taste of MSG, was found. Its terminal pyridine residue and linear structure are suggested to be responsible for its strong activity. The time taken to reach maximum taste intensity exhibited by it, as determined by the time-intensity method, is 22.0 s, whereas the maximum taste intensity of MSG occurs immediately. This distinct difference in the time-course taste profile may be due to the hydrophobicity and strong receptor affinity of the new compound.

Synthesis of sorbicillinoid analogues with anti-inflammation activities

Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.

Cinnamyl carboxylate compound and application thereof

The invention discloses a cinnamyl carboxylate compound and application of agriculturally acceptable salt thereof as a herbicide. The compound is shown as a general formula (I), wherein substituent groups in the general formula (I) are defined in the spec

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.

Modular Cyclopentenone Synthesis through the Catalytic Molecular Shuffling of Unsaturated Acid Chlorides and Alkynes

We describe a general strategy for the intermolecular synthesis of polysubstituted cyclopentenones using palladium catalysis. Overall, this reaction is achieved via a molecular shuffling process involving an alkyne, an α,β-unsaturated acid chloride, which serves as both the alkene and carbon monoxide source, and a hydrosilane to create three new C-C bonds. This new carbon monoxide-free pathway delivers the products with excellent yields. Furthermore, the regioselectivity is complementary to conventional methods for cyclopentenone synthesis. In addition, a set of regio- and chemodivergent reactions are presented to emphasize the synthetic potential of this novel strategy.

USE OF PHYSIOLOGICAL COOLING ACTIVE INGREDIENTS, AND COMPOSITIONS COMPRISING SUCH ACTIVE INGREDIENTS

The invention relates primarily to a method of modulation, preferably of in vitro and/or in vivo modulation, of the cold menthol receptor TRPM8, wherein the receptor is contacted with at least one modulator selected from the group consisting of the compounds of the structure type 1 described herein. The present invention further relates to corresponding uses and compositions comprising such compounds.

Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease

Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity. Herein, a series of carboline-cinnamic acid hybrids was designed and synthesized to obtain new multifunctional molecules with low toxicity and good physicochemical properties. In particular, e3 and e12 exhibited significant inhibition of Aβ aggregation (inhibitory rate at 25 μM: 65% and 72% respectively), moderate BuChE inhibition, excellent neuroprotective effects and low neurotoxicity. Furthermore, in the AD mice model, e3 and e12 could restore learning and memory function to a comparable level to that of the control and did not exhibit any acute toxicity in vivo at a relatively high dose of 600 mg/kg. Thus, these new compounds can be further studied as multifunctional molecules for AD.

Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones

Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.

Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors. We have synthesized twenty four derivatives, characterized and evaluated their 5-LOX inhibition potential. Coumaperine derivatives substituted with multiple hydroxy and multiple methoxy groups exhibited best 5-LOX inhibition. CP-209, a catechol type dihydroxyl derivative and CP-262-F2, a vicinal trihydroxyl derivative exhibited, 82.7% and 82.5% inhibition of 5-LOX respectively at 20 μM. Their IC50 values are 2.1 ± 0.2 μM and 2.3 ± 0.2 μM respectively, and are comparable to zileuton, IC50 = 1.4 ± 0.2 μM. CP-155, a methylenedioxy derivative (a natural product) and CP-194, a 2,4,6-trimethoxy derivative showed 76.0% and 77.1% inhibition of 5-LOX respectively at 20 μM. Antioxidant study revealed that CP-209 and 262-F2 (at 20 μM) scavenged DPPH radical by 76.8% and 71.3% respectively. On the other hand, CP-155 and 194 showed very poor DPPH radical scavenging activity. Pseudo peroxidase assay confirmed that the mode of action of CP-209 and 262-F2 were by redox process, similar to zileuton, affecting the oxidation state of the metal ion in the enzyme. On the contrary, CP-155 and 194 probably act through some other mechanism which does not involve the disruption of the oxidation state of the metal in the enzyme. Molecular docking of CP-155 and 194 to the active site of 5-LOX and binding energy calculation suggested that they are non-competitive inhibitors. The In-Silico ADME/TOX analysis shows the active compounds (CP-155, 194, 209 and 262-F2) are with good drug likeliness and reduced toxicity compared to existing drug. These studies indicate that there is a great potential for coumaperine derivatives to be developed as anti-inflammatory drug.

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

A general synthetic route to the unknown 1,3-dicarbonyl tropane derived curcumin analogues was developed. The method was based on the aldol condensation reaction (40–90 % yield, two steps without product isolation) and acylation of the resulting 2-benzylidenetropinones with substituted cinnamoyl cyanides (yields 41–91 %). Overall 18 new tropane derivatives featuring the characteristic curcuminoid hepta-1,6-dien-3,5-dione structure were synthesized and characterized. The range of the substituted aromatic rings in the prepared analogues included Ph, m-MeO-C6H4, 3,4-di-MeO-C6H3, 3,4,5-tri-MeO-C6H2, p-Br-C6H4, p-F-C6H4, p-CF3-C6H4, p-NO2-C6H4, 2-NO2-4,5-di-CH3O-C6H2, 2-NO2-4,5-O-CH2-O-C6H2, 3-MeO-4-[CH(CH3)-OEt]-C6H3, 3-MeO-4-OH-C6H3, p-MeO-C6H4, 4,5-O-CH2-O-C6H3, 3-MeO-4-MeOCOO. Two orthogonal protective groups for hydroxyl (acetal or carbonate), removable in acidic or basic conditions, were used for synthesizing curcuminoids with free phenolic groups (3-MeO-4-OH-C6H3).