Α-phenylcinnamic Acid Research Articles

Integrated application of transcriptomics and metabolomics provides insights into the antifungal activity of α-phenylcinnamic acid against Colletotrichum gloeosporioides

Anthracnose caused by Colletotrichum gloeosporioides leads to significant economic loss of varieties of tropical and subtropical fruit. In the present study, a cinnamic acid derivative α-phenylcinnamic acid (α-PA) was found effective in control of postharvest anthracnose on mango fruit. α-PA strongly inhibited conidia germination, germ tube elongation, and appressorium formation. To elucidate the underlying molecular mechanisms by which α-PA shows antifungal activity, a transcriptomics and a widely targeted metabolomics analysis were conducted to study the changes in gene expression and metabolic profile. The result showed that the expression of 1477 genes and content of 198 metabolites were changed by α-PA. The following KEGG enrichment and correlation analysis suggested that biosynthesis of amino acids and some secondary metabolites were interfered by α-PA, including indoles which are one group of melanin precursors. In addition, qRT-PCR analysis and measurement of melanin revealed that α-PA down-regulated the expression of melanin biosynthesis genes and reduced melanin biosynthesis. Taken together, these data suggest that α-PA could decrease anthracnose in postharvest fruit by interfere with amino acid and secondary metabolite metabolism of C. gloeosporioides.

Electrocatalytic asymmetric hydrogenation of α,β-unsaturated acids in a PEM reactor with cinchona-modified palladium catalysts

We have developed an electrocatalytic asymmetric hydrogenation reaction using a proton-exchange membrane (PEM) reactor that employs a polymer electrolyte fuel cell and industrial electrolysis technologies. Reasonable enantioselectivities and excellent current efficiencies were obtained in the asymmetric hydrogenation of α-phenylcinnamic acid under mild conditions without adding a supporting electrolyte. The current density was crucial to achieving the improved results observed.

Kinetic analysis of the asymmetric hydrogenation of (E)-2,3-diphenylpropenoic acid over cinchonidine derivative-modified Pd/C: quinoline ring modification

The substitutions at the 2′- and/or 6′-positions of the quinoline ring of cinchonidine reduce both the intrinsic enantioselectivity and adsorption strength for the enantioselective hydrogenation of α-phenylcinnamic acid over Pd/C.

Direct Synthesis of in-Situ Chirally Modified Palladium Nanocrystals without Capping Agents and Their Application in Heterogeneous Enantioselective Hydrogenations

Shape-controlled metal nanocrystals possess the advantages of specific atomic arrangement on the surface and uniform size, which can act as ideal model catalysts for heterogeneous enantioselective catalytic studies. Nevertheless, capping agents are commonly retained on the surface of the as-synthesized metal nanocrystals, which may hinder the necessary interaction between the substrate and the chiral modifiers coadsorbed on the metal surface for chiral recognition. In this paper, we directly synthesized dendritic or cubic palladium nanocrystals in-situ modified by chiral modifiers such as cinchonidine (CD) or S-proline through a one-pot strategy by replacing the conventional capping agents with the chiral modifiers. The as-prepared CD-modified Pd nanodendrite catalyst already exhibits enantioselectivity in the asymmetric hydrogenation of (E)-α-phenylcinnamic acid without subsequent chiral modification processes. The in-situ S-proline-modified Pd nanocube catalyst shows higher enantioselectivity than nanoc...

Cascade Reactions of α‐Phenylcinnamic Acid to Polycyclic Compounds Promoted by High Valent Transition Metal Halides

Abstractα‐Phenylcinnamic acid converts into polycyclic derivatives by interaction with high valent transition metal halides in chloroform at reflux temperature. Different products, featured by local structural differences depending on the nature of the metal halide system (i. e. WCl6, PCl5/NbF5 or PCl5/NbCl5), are easily isolable after treatment with water. In particular, WCl6 configures as an efficient multitasking agent, working as 1) chlorinator of the carboxylic acid function, 2) catalytic precursor for intra‐ and intermolecular rearrangements, and 3) catalytic precursor for Baeyer‐Villiger lactonization in water at ambient temperature, exploiting air as oxidant. The products have been purified by alumina chromatography, and identified by analytical and spectroscopic (IR, NMR) techniques, and by single crystal X‐ray diffraction in three cases. Their formation probably involves a common reaction pathway which has been rationalized by DFT calculations.

Design, synthesis, and biological evaluation of novel combretastatin A-4 thio derivatives as microtubule targeting agents

A series of novel combretastatin A-4 (CA-4) thio derivatives containing different molecular cores, namely α-phenylcinnamic acids (core 1), (Z)-stilbenes (core 2), 4,5-disubstituted oxazoles (core 3), and 4,5-disubstituted N-methylimidazoles (core 4), as cis-restricted analogues were designed and synthesized. They were selected with the use of a parallel virtual screening protocol including the generation of a virtual combinatorial library based on an elaborated synthesis protocol of CA-4 analogues. The selected compounds were evaluated for antiproliferative activity against a panel of six human cancer cell lines (A431, HeLa, MCF7, MDA-MB-231, A549 and SKOV) and two human non-cancer cell lines (HaCaT and CCD39Lu). Moreover, the effect of the test compounds on the inhibition of tubulin polymerization in vitro was estimated. In the series studied here, oxazole-bridged analogues exhibited the most potent antiproliferative activity. Compounds 23a, 23e, and 23i efficiently inhibited tubulin polymerization with IC50 values of 0.86, 1.05, and 0.85 μM, respectively. Thio derivative 23i, when compared to its oxygen analogue 23j, showed a 5-fold higher inhibitory impact on tubulin polymerization. Compounds 23e and 23i, which showed both best cytotoxic and antitubulin activity, were further studied in terms of their effect on cell cycle distribution and proapoptotic activity. Compound 23e induced a statistically significant block of the cell cycle at the G2/M phase in A431, HaCaT, HeLa, MCF-7, MDA-MB-231, and SKOV-3 cells to an extent comparable to that observed in CA-4. In HeLa and SKOV-3 cells incubated with 23i, a concentration-dependent block of the G2/M phase was observed. The proapoptotic effect of 23e and 23i in A431, HaCaT, MCF-7, MDA-MB-231, and SKOV-3 was demonstrated with ELISA assay and double staining with Annexin V-FITC/PI. The results indicated that compound 23e and 23i may serve as novel lead compounds in research on more effective anticancer agents.

Structure-performance relationships of phenyl cinnamic acid derivatives as MALDI-MS matrices for sulfatide detection.

A key aspect for the further development of matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (MS) is a better understanding of the working principles of MALDI matrices. To address this issue, a chemical compound library of 59 structurally related cinnamic acid derivatives was synthesized. Potential MALDI matrices were evaluated with sulfatides, a class of anionic lipids which are abundant in complex brain lipid mixtures. For each matrix relative mean S/N ratios of sulfatides were determined against 9-aminoacridine as a reference matrix using negative ion mass spectrometry with 355 and 337nm laser systems. The comparison of matrix features with their corresponding relative mean S/N ratios for sulfatide detection identified correlations between matrix substitution patterns, their chemical functionality, and their MALDI-MS performance. Crystal structures of six selected matrices provided structural insight in hydrogen bond interactions in the solid state. Principal component analysis allowed the additional identification of correlation trends between structural and physical matrix properties like number of exchangeable protons at the head group, MW, logP, UV-Vis, and sulfatide detection sensitivity. Graphical abstract Design, synthesis and mass spectrometric evaluation of MALDI-MS matrix compound libraries allows the identification of matrix structure - MALDI-MS performance relationships using multivariate statistics as a tool.

EXAFS Characterization of Pd Catalysts for Enantioselective Hydrogenation of α-Phenylcinnamic Acid: Pretreatment Effects and Thiol Adsorption

The effects of the pretreatment and Pd-distribution on the enantioselective hydrogenation of α-phenylcinnamic acid over cinchonidine-modified Pd/C and Pd/Al2O3 were studied by use of EXAFS techniques combined with thiol adsorption. It is suggested that the enhanced performance by the H2-pretreatment at 353 K is ascribed to the elimination of contaminants and/or H2O from Pd/C. The Pd–S CN is related to the Pd dispersion and the reactivity and diffusivity of thiols used.

Adsorption and Performance of Chiral Cinchona Alkaloid Modifiers over Pd/C Catalyst for Enantioselective Hydrogenation of α-Phenylcinnamic Acids

Abstract The enantioselective hydrogenation reactions of α-phenylcinnamic acid (PCA) and 4,4′-dimethoxy α-phenylcinnamic acid (DMPCA) were carried out over chiral cinchona alkaloid-modified Pd/C. Two sets of the modifiers were employed to get deeper insights into the effects of relative adsorption strength between the modifier and the substrate on the enantioselectivity; cinchonidine (CD)/cinchonine (CN) and quinine (QN)/quinidine (QD). The performances of the two sets of modifiers were compared by systematically varying the modifier concentration over a wide range. It was clearly substantiated that the origin of the low selectivity observed with QN/QD at an ordinary concentration is primarily due to its weak adsorption strength on Pd metal surface, which originates from the steric hindrance of the methoxy substituent at C6. A new modifier, 6-hydroxy CD, was found to exhibit a performance comparable to that of CD, implying that the steric hindrance of the 6-methoxy group of QN/QD is much more influential than the electronic effects.

Enantioselective hydrogenation of α-phenylcinnamic acids over cinchonidine-modified Pd/C commercial catalysts

Enantioselective hydrogenation of α-phenylcinnamic acid (PCA) and p,p′-dimethoxyphenylcinnamic acid (DMPCA) was studied over a variety of commercial 5 % Pd/C catalysts to reveal catalyst properties suitable for obtaining high enantioselectivity. The catalysts were characterized by CO adsorption, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). It is confirmed that pretreatment at 353 K under atmospheric pressure of H2 before modification with cinchonidine is very effective for all the Pd/C catalysts used here to improve the selectivity and reaction rate. It is suggested that the distribution of Pd metal particles is crucial to attain high selectivity (ee% = 79 ± 1 for PCA, 89 ± 2 for DMPCA): a uniform or eggshell-type distribution of Pd is more suitable than an egg-white or egg-yolk-type distribution. It is also suggested that the dispersion of Pd metal particles controls the enantioselectivity over cinchonidine (CD)-modified Pd/C catalysts. XPS techniques are proposed to provide a convenient method to find desirable catalysts. The choice of such Pd/C catalysts could facilitate high-throughput guided study on highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids.

Carbonaceous materials as catalyst supports for the enantioselective hydrogenation of (E)-α-phenylcinnamic acid: Effect of the support acidity

A systematic comparative study of carbonaceous materials as catalyst supports for the asymmetric heterogeneous hydrogenation of (E)-α-phenylcinnamic acid (PCA) was performed to investigate the influence of the supports on the enantioselectivity. A series of Pd-based catalysts supported on activated carbon (AC), graphene oxide (GO), or carbon nanotubes (CNTs) was prepared using deposition methods. The hydrogenation reactions of PCA were conducted with/without the pretreatment of the prepared catalysts, and the results showed a significant drop of enantiomeric excess (ee) when the Pd/GO catalyst was used (27%) compared to that obtained from the Pd/AC (70%) and Pd/CNTs (66%) catalysts. This drop of ee values was assigned to the abundance of acidic sites present on the Pd/GO catalyst, as revealed by TGA, FT-IR, and TPD–NH3 analyses. The effect of the support acidity on the ee was ascribed to the preferential adsorption mode of cinchonidine (CD) on the GO surface via electrostatic interactions between the negatively charged oxygen functional groups present on the GO surface and the positively protonated amine groups of the CD molecule.

The enantioselective hydrogenation of (E)-α-phenylcinnamic acid: Role of TiO2 coated on Al2O3 as a novel support for cinchonidine-modified Pd catalysts

The TiO2-coated Al2O3 composites with various TiO2 wt.% loadings were synthesized by the sol–gel method and were used as supports for the Pd-based catalysts to evaluate the enantiomeric excess (ee) of the hydrogenation of (E)-α-phenylcinnamic acid. The physicochemical properties of the composites and the Pd-based catalysts were characterized. The results reveal the strong influence of the TiO2 wt.% loading on the ee value, which is attributed to the effect of pore diffusion. The 5%TiO2/Al2O3 support, which can diminish most of small mesopores in Al2O3 template while remain most of large mesopores, exhibits the highest ee. Our results demonstrate the promising application of mixed oxides as novel supports to improve ee values of the asymmetric hydrogenation of unsaturated prochiral compounds.

Palladium nanocarbon catalysts (Pd/CNT) as potential enantioselective heterogeneous systems. The behavior in the hydrogenation and hydroarylation of unsaturated substrates

Hydroxy-CNT were modified with optically active α-amino acids. The resulting chiral derivatives were directly palladated with Pd2dba3 and used to catalyze the hydrogenation of α-acetamidostyrene and α-phenylcinnamic acid as well as the hydroarylation of norbornene with iodoarenes. All the catalytic reactions afforded products containing a new chiral carbon center in high yields, though as racemates. Apparently, asymmetric induction is precluded because the palladium sites on the CNT surface are spatially apart from the chiral carbon centers in amino acid groups.

Kinetic and Stereochemical Analyses of Amine-Additive Effects on the Hydrogenation of α-Phenylcinnamic Acid over Cinchonidine-Modified Pd/C

Abstract Asymmetric hydrogenation of α-phenylcinnamic acid catalyzed by cinchonidine (CD)-modified palladium has been performed. Without benzylamine (BA), a modification inconsistency was observed: the rate diminished when a small amount of CD was used, whereas the product enantiomeric excess (ee) increased when substantially more CD was used. By altering the amount of amine additive, we deduced that this inconsistency was caused by the amine effect of CD itself. With a 1,8-diazabicyclo[5.4.0]undec-7-ene additive, the catalytic amount was sufficient to result in the highest ee of 81%.

Induction period for the enantioselective hydrogenation of α,β-unsaturated acids over a cinchonidine-modified palladium catalyst

The enantioselective hydrogenation of α-phenylcinnamic acid (PCA) was performed using a cinchonidine (CD)-modified Pd/C catalyst, and the conversion and enantiomeric excess (ee) of the product were monitored during the reaction. Low ee values were observed only during the initial stages of the reaction (<20 % conversion) in the presence of benzylamine as reported, and the use of the 3-ethyl-analogue instead of 3-vinyl natural CD as a modifier resulted in no decline in ee despite the presence of amine. Because the 3-ethyl moiety was generated in situ during the modification process prior to the reaction of PCA, the role of the 3-substituent was unclear, as is the case with Pt/ketone hydrogenation systems. To determine the reasons for the induction, the initial stage of the reaction was mimicked using a very small amount of substrate (stoichiometric catalysis). During this study, a minimum quantity of benzylamine additive was found to be necessary to increase the ee and the reaction rate, indicating that benzylamine functioned during the induction period.

Anomalous Ligand Acceleration on Cinchona-modified Pd/C during Asymmetric Hydrogenation of Properly Substituted Phenylcinnamic Acid

Abstract The hydrogenation of 4,4′-dimethoxy-α-phenylcinnamic acid over Pd/C showed a large ligand acceleration effect when a cinchonidine modifier was used; the hydrogen rate increased to 370% relative to the reaction rate on unmodified Pd/C and resulted in a 91% enantiomeric excess (ee). Another good substrate, 4-fluoro-2′-methoxyphenylcinnamic acid, also resulted in a high ee value of 92%; however, the rate increased only to 230% when this modifier was used. On the basis of the difference in the degree to which the reaction rate was accelerated, the eemax for each substrate was analyzed.

Preparation of Pd/C designed for chiral modified catalyst: Comparison with Pd/TiO2 in enantioselective hydrogenation of α-phenylcinnamic acid

Enantioselective hydrogenation of α-phenylcinnamic acid was investigated on Pd/C catalysts prepared in our laboratory to compare activity and selectivity with those on commercial Pd/C and Pd/TiO2 catalysts. The Pd/C catalysts after the 353 K-H2-pretreatment exhibited satisfactory and comparable performances obtained with commercially available best ever Pd/C by optimizing catalyst preparation. In contrast to Pd/TiO2, a high loading of Pd is not necessary with Pd/C, but only 5% loading on a certain activated carbon was found to result in high e.e. It is suggested that the optimum size or size-distribution of Pd metal particle are different between the two supports, suggesting a support effect of this catalyst system.

Preliminary Evaluation of Anticonvulsant Activity of Some Aminoalkanol and Amino Acid Cinnamic Acid Derivatives

A series of aminoalkanol and amino acid derivatives of trans-cinnamic acid as well as aminoalkanol derivatives of �-phenylcinnamic acid was synthesized and evaluated for anticonvulsant activity. All compounds were verified in mice after intraperitoneal (i.p.) administration in maximal electroshock (MES) and subcutaneous pentetrazole (ScMet) induced seizures as well as neurotoxicity assessment. Six of them showed protection in MES at 100 mg/kg b.w. and one at 300 mg/kg b.w. For selected derivatives evaluation in ScMet test in rats after per os (p.o.) administration, 6-Hz test in mice and pilocarpine-induced status in rats were performed. The results are quite encouraging and further modification of the structures might lead to discovering new potential anticonvulsants.

Efficient synthesis of hydroxystyrenes via biocatalytic decarboxylation/deacetylation of substituted cinnamic acids by newly isolated Pantoea agglomerans strains

Decarboxylation of substituted cinnamic acids is a predominantly followed pathway for obtaining hydroxystyrenes-one of the most extensively explored bioactive compounds in the food and flavor industry (e.g. FEMA GRAS approved 4-vinylguaiacol). For this, mild and green strategies providing good yields with high product selectivity are needed. Two newly isolated bacterial strains, i.e. Pantoea agglomerans KJLPB4 and P. agglomerans KJPB2, are reported for mild and effective decarboxylation of substituted cinnamic acids into corresponding hydroxystyrenes. Key operational parameters for the process, such as incubation temperature, incubation time, substrate concentration and effect of co-solvent, were optimized using ferulic acid as a model substrate. With strain KJLPB4, 1.51 g L⁻¹ 4-vinyl guaiacol (98% yield) was selectively obtained from 2 g L⁻¹ ferulic acid at 28 °C after 48 h incubation. However, KJPB2 provided vanillic acid in 85% yield after 72 h following the oxidative decarboxylation pathway. In addition, KJLPB4 was effectively exploited for the deacetylation of acetylated α-phenylcinnamic acids, providing corresponding compounds in 65-95% yields. Two newly isolated microbial strains are reported for the mild and selective decarboxylation of substituted cinnamic acids into hydroxystyrenes. Preparative-scale synthesis of vinyl guaiacol and utilization of renewable feedstock (ferulic acid extracted from maize bran) have been demonstrated to enhance the practical utility of the process.

ChemInform Abstract: Effect of Support Texture on Enantioselective Hydrogenation of (E)-α-Phenylcinnamic Acid with Cinchonidine-Modified Palladium Catalysts.

The texture of support materials has decisive influence on the behavior of cinchonidine-modified palladium catalysts in the enantioselective hydrogenation of (E)-α-phenylcinnamic acid, which suggests an important role of pore diffusion in the determination of the selectivity. Palladium metal particles located in micropores of the support have detrimental effect; nonporous ultra fine materials are preferable.