Cinnamoyl Moiety Research Articles

Hydroxycinnamoyltransferases in plant metabolism

Hydroxycinnamoyltransferases are enzymes transferring hydroxycinnamoyl units like cinnamoyl, 4-coumaroyl, caffeoyl, feruloyl and sinapoyl moieties from an activating residue such as coenzyme A or glucose or activated as hydroxycinnamoyl ester (e.g. chlorogenate) to an acceptor molecule, most commonly to an OH or NH2 group as ester or amide. The hydroxycinnamoyl groups play either a “decorating” role or are building blocks of more complex structures. Proteins catalysing hydroxycinnamoyl transfer have been known for many decades and are nowadays investigated on molecular and structural levels. At least four different protein families give rise to enzymes with hydroxycinnamoyltransferase activity: serine carboxypeptidase-like proteins, tyramine hydroxycinnamoyltransferase-like enzymes, BAHD acyltransferases and GDSL-lipase/esterase-like enzymes. Interestingly, the same or very similar products can be formed by enzymes from different enzyme classes and using differently activated hydroxycinnamoyl units. This review will summarise the current literature data on the features of hydroxycinnamoyltransferases from the four different enzyme groups.

N-Cinnamoylation of Antimalarial Classics: Effects of Using Acyl Groups Other than Cinnamoyl toward Dual-Stage Antimalarials.

In a follow-up study to our reports of N-cinnamoylated chloroquine and quinacrine analogues as promising dual-stage antimalarial leads with high in vitro potency against both blood-stage Plasmodium falciparum and liver-stage Plasmodium berghei, we decided to investigate the effect of replacing the cinnamoyl moiety with other acyl groups. Thus, a series of N-acylated analogues were synthesized, and their activities against blood- and liver-stage Plasmodium spp. were assessed along with their in vitro cytotoxicities. Although the new N-acylated analogues were found to be somewhat less active and more cytotoxic than their N-cinnamoylated counterparts, they equally displayed nanomolar activities in vitro against blood-stage drug-sensitive and drug-resistant P. falciparum, and significant in vitro liver-stage activity against P. berghei. Therefore, it is demonstrated that simple N-acylated surrogates of classical antimalarial drugs are promising dual-stage antimalarial leads.

Reaction of Nitromethane with Cinnamoyl Derivatives of Cyclic β-dicarbonyl Compounds. Application to the Synthesis of 2(3)-(4-aryl-pyrrolidin-2-ylidene)-1,3(2,4)-diones*

We have shown that reaction of nitromethane with cinnamoyl derivatives of five- and six-membered carbo- and heterocylic β-dicarbonyl compounds in the presence of 1,1,3,3-tetramethylguanidine proceeds according to the mechanism of 1,4-conjugate addition to the enone fragment of cinnamoyl moiety to give 2(3)-( 3-aryl-4-nitrobutanoyl)-substituted cyclic 1,3- or 2,4-diones in good to excellent yields. Chemoselective reduction of nitro function of the latter leads to synthetically useful and biologically interesting 2(3)-(4-arylpyrrolidin-2-ylidene) derivatives.

Reversible Cross-Linking of Aliphatic Polyamides Bearing Thermo- and Photoresponsive Cinnamoyl Moieties

Photosensitive polymers have gained strong attention in development of different polymeric systems for diverse applications. Particular attention is paid to polymers with cinnamoyl groups either in polymer backbone or in pendent position owing to their excellent photoreactivity and thermoreactivity upon UV light irradiation or heating. This work aims at synthesizing a novel photo- and thermosensitive aliphatic polyamide by anionic ring-opening copolymerization of ε-caprolactam and α-cinnamoylamido-ε-caprolactam. The photochemical reversible cross-linking of solutions and thermal cross-linking of spin-coated films made up of these new cinnamoyl-functionalized polyamides were monitored by UV–vis spectroscopy. These aliphatic polyamide copolymers were characterized by magic angle spinning solid-state NMR, and their thermal behaviors were studied by thermogravimetric analysis, differential scanning calorimetry, and dynamic mechanical analysis.

Design, synthesis and SAR analysis of antitumour styryl lactones related to (+)-crassalactones B and C

A series of styryl lactones containing the cinnamic acid ester groups such as (+)-crassalactones B (3a) and C (4a), 5,7-di-O-cinamoyl derivative 6, the corresponding 7-epimers and 7-deoxy derivatives have been synthesized, characterized and evaluated for their in vitro antitumour activity against a panel of several human tumour cell lines. Twelve new analogues such as 5-O- or 7-O-(4-methoxycinnamoyl), 5-O- or 7-O-(4-nitrocinnamoyl) and 5-O- or 7-O-(4-fluorocinnamoyl) esters of (+)-goniofufurone (3b–d), 7-epi-(+)-goniofufurone (epi-3b–d), as well as 7-deoxy derivatives 5b–d have been prepared to correlate all compounds in a SAR study. Some of the analogues displayed powerful antiproliferative effects on selected human tumour cell lines, but none of them demonstrated cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). Thus, for the 7-epi-crassalactone B (epi-3a) was found to be a potent inhibitor of HL-60 cells growth, with an IC50 value that is approximately 46-fold lower than that observed for the commercial antitumour drug doxorubicin in the culture of the same cells. A SAR analysis performed on these lactones reveals the main structural features that affect their antiproliferative activity, such as nature of the substituents at the C-4 in the aromatic rings of cinnamoyl moieties, the absolute stereochemistry, as well as the presence of a deoxy function at the C-7 position.

Investigation of acyl migration in mono- and dicaffeoylquinic acids under aqueous basic, aqueous acidic, and dry roasting conditions.

Acyl migration in chlorogenic acids describes the process of migration of cinnamoyl moieties from one quinic acid alcohol group to another, thus interconverting chlorogenic acid regioisomers. It therefore constitutes a special case of transesterification reaction. Acyl migration constitutes an important reaction pathway in both coffee roasting and brewing, altering the structure of chlorogenic acid initially present in the green coffee bean. In this contribution we describe detailed and comprehensive mechanistic studies comparing inter- and intramolecular acyl migration involving the seven most common chlorogenic acids in coffee. We employe aqueous acidic and basic conditions mimicking the brewing of coffee along with dry roasting conditions. We show that under aqueous basic conditions intramolecular acyl migration is fully reversible with basic hydrolysis competing with acyl migration. 3-Caffeoylquinic acid was shown to be most labile to basic hydrolysis. We additionally show that the acyl migration process is strongly pH dependent with increased transesterification taking place at basic pH. Under dry roasting conditions acyl migration competes with dehydration to form lactones. We argue that acyl migration precedes lactonization, with 3-caffeoylquinic acid lactone being the predominant product.

29.3: Performance of Novel LC‐Photo‐Aligning Cinnamoyl Side‐Chain Polymers

AbstractWe present two types of novel side‐chain photo‐polymers with cinnamoyl moieties for photo‐alignment and patterning of the alignment of liquid crystal displays (LCDs). One type is designed for photo‐thermal processing; the other comprises co‐polymer side‐chain functions combining room temperature photo‐processing with excellent image sticking. The planar aligning materials are highly UV sensitive (315nm, 150mJ/cm2). They target in‐plane switched (IPS)‐LCDs with excellent AC‐image sticking, comparable to brushed polyimides. Correlations between photo‐dimerization and image sticking are discussed.

Stereochemistry and Conformation of Skyllamycin, a Non‐Ribosomally Synthesized Peptide from Streptomyces sp. Acta 2897

Skyllamycin is a non-ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF-signaling. The peptide scaffold contains an N-terminal cinnamoyl moiety, a β-methylation of aspartic acid, three β-hydroxylated amino acids and one rarely occurring α-hydroxy glycine. With the exception of α-hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC-MS and Marfey-HPLC analysis. The stereochemistry of α-hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY-NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R- and S-configured α-hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S-configured α-hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two-component flavin dependent monooxygenase (Sky39) as S-selective.

Synthesis and Properties of a Novel Spirooxazine Dye

A novel bifunctional photochromic compound 2 based on spirooxazine and cinnamoyl moiety was synthesized by esterification reaction. Its structure was characterized by 1 H NMR, 13 C NMR, IR and X-ray single crystal diffraction. The compound was proved by UV testing to have excellent photochromic properties both in organic solvents and polymer films when irridiated with high pressure Hg lamp. The acidichromism phenomenon of compound 2 was studied too. No significant fluorescence emission of compound 2 was observed in EtOH solution before and after irradiation. Under the acidic condition or irradiation with 150 W Xe lamp, The ethanol solution of compound 2 exhibits a good fluorescence respectively. The ethanol solution of compound 2 exhibits obvious fluorescence emission. After irradiating the acidic solution, new fluorescence emis- sion can be observed. The emission change modulated by acid or light offers compound 2 to be potential as a new fluorescent molecular switch. Keywords spirooxazine; photochromism; cinnamate; acidichromism; fluorescence

Structure-Reactivity Correlations in Nucleophilic Displacement Reactions of Y-Substituted-Phenyl X-Substituted-Cinnamates with Z-Substituted-Phenoxides

Second-order rate constants (<TEX>$k_N$</TEX>) have been measured spectrophotometrically for the nucleophilic displacement reactions of 4-nitrophenyl X-substituted-cinnamates (4a-4e) and Y-substituted-phenyl cinnamates (5a-5e) with Z-substituted-phenoxide anions in 80 mol % <TEX>$H_2O$</TEX>/20 mol % DMSO at <TEX>$25.0{\pm}0.1^{\circ}C$</TEX>. The Hammett plot for the reactions of 4a-4e with 4-chlorophenoxide (4-<TEX>$ClPhO^-$</TEX>) consists of two intersecting straight lines, which might be taken as a change in the rate-determining step (RDS). However, it has been concluded that the nonlinear Hammett plot is not due to a change in the RDS but is caused by stabilization of the ground state of substrates possessing an electron-withdrawing group in the cinnamoyl moiety through resonance interactions, since the Yukawa-Tsuno plot exhibits an excellent linear correlation with <TEX>${\rho}X=0.89$</TEX> and r = 0.58. The Br<TEX>${\o}$</TEX>nsted-type plot for the reactions of 4-nitrophenyl cinnamate (4c) with Z-substituted-phenoxides is linear with <TEX>${\beta}_{nuc}=0.76$</TEX>. The Br<TEX>${\o}$</TEX>nsted-type plot for the reactions of Y-substituted-phenyl cinnamates (5a-5d) with 4-chlorophenoxides (4-<TEX>$ClPhO^-$</TEX>) is also linear with <TEX>${\beta}_{lg}=-0.72$</TEX>. The Hammett plot correlated with <TEX>${\sigma}^-$</TEX> constants for the reactions of 5a-5d results in a much better linear correlation than that correlated with <TEX>${\sigma}^o$</TEX> constants, indicating that a partial negative charge develops on the O atom of the leaving aryloxide. Thus, the reactions have been concluded to proceed through a concerted mechanism.

Dispersibility and Emulsion-Stabilizing Effect of Cellulose Nanowhiskers Esterified by Vinyl Acetate and Vinyl Cinnamate

The surface of cotton cellulose nanowhiskers (CNW's) was esterified by vinyl acetate (VAc) and vinyl cinnamate (VCin), in the presence of potassium carbonate as catalyst. Reactions were performed under microwave activation and monitored by Fourier transform infrared (FT-IR) spectroscopy. The supramolecular structure of CNW's before and after modification was characterized by X-ray diffraction (XRD) and atomic force microscopy (AFM). Distinctively from the acetylation treatment, an increase in particles dimensions was noted after esterification with VCin, which was assigned to π-π stacking interactions that may exist between cinnamoyl moieties. The dispersibility and emulsion stabilizing effect of acylated CNW's was examined in ethyl acetate, toluene, and cyclohexane, three organic solvents of medium to low polarity. The acylated nanoparticles could never be dispersed in toluene nor cyclohexane, but they formed stable dispersions in ethyl acetate while remaining dispersible in water. Stable ethyl acetate-in-water, toluene-in-water, and cyclohexane-in-water emulsions were successfully prepared with CNW's grafted with acetyl moieties, whereas the VCin-treated particles could stabilize only the cyclohexane-in-water emulsions. The impact of esterification treatment on emulsion stability and droplets size was particularly discussed.

New photosensitive semi aramid/organoclay nanocomposite containing cinnamoyl groups: Synthesis and characterization

New poly(ether–amide)/layered silicate nanocomposites (PEAN) containing dibenzalacetone and cinnamoyl moieties were prepared via solution intercalation technique from poly(ether–amide) 6 and organo-MMT in a solution of N,N-dimethylacetamide (DMAc). New dicarboxylic acid 4 was synthesis from two step reactions. At first 4,4′-bis(1,4-diphenoxybutane) dialdehyde 3 was synthesized from 1,4-dibromobutane and 4-hydroxybenzaldehyde, then solvent free reaction using to synthesis 4,4′-bis(1,4-diphenoxybutane) diacrylic acid from dialdehyde 3 and malonic acid. Poly(ether–amide) (PEA) chains were synthesized from 4,4′-bis(1,4-diphenoxybutane)diacrylic acid 4 and 2,5-bis(4-aminobenzylidene)cyclopentanone 5 via a direct polycondensation reaction. The synthesized PEA was characterized by Fourier transform infrared spectra (FTIR), nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC) and UV–Vis spectroscopy. The distribution of organoclay and nanostructure of the nanocomposites were investigated by X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses. The thermal properties and flammability of the nanocomposites were investigated by thermogravimetric analysis (TGA), differential scanning calorimetric (DSC) and microscale combustion calorimeter (MCC). In the presence of organoclay shows a good effect on improving the flame retardancy of the PEA, reflecting the decrease in heat release rate (HRR) and the total heat release (THR) of the nanocomposites, while the thermal stability of nanocomposites only changed slightly compared to the neat polymer. With the increase of the loading of organoclay, the nanocomposites showed improved flame retardancy and higher char residues.

Refractive Index Change during Photo Crosslinking Reaction of Poly (silsesquioxane) Derivatives Containing Cinnamoyl Moieties in the Side Chains

Refractive Index Change during Photo Crosslinking Reaction of Poly (silsesquioxane) Derivatives Containing Cinnamoyl Moieties in the Side Chains

Photoalignment of liquid crystals by a covalently attached self-assembled ultrathin film

In this paper, the polyanion-containing cinnamoyl group (PACSS-CF3) was self-assembled with diazoresin (DR) to form a kind of stable covalent ultrathin film by irradiation with 365 nm UV light. The photoalignment properties of the DR/PACSS-CF3 covalent film were investigated. The covalent film was found to have anisotropy after irradiation by 297 nm linearly polarised ultraviolet light (LPUVL), and could induce uniform alignment of liquid crystals (LCs). The pretilt angle of the LC was 2.5°. The stability of the film was enhanced by the covalent bonds. The films were thermally stable to 180°C. Polarised UV-Vis spectroscopy was utilised to investigate the photochemical process of the covalent film. It was found that cinnamoyl moieties parallel to the polarisation direction of the LPUVL were consumed by the photoreaction faster than those perpendicular to the polarisation direction. It can be concluded that the selective photoreaction induced the anisotropy of the films. The anisotropic films induced the homogeneous alignment of LC.

Synthesis of novel photochromic spiropyran dyes containing quaternary ammonium salt or cinnamoyl moiety and their properties as photoinitiators

AbstractThree novel spiropyran (SP) dyes containing quaternary ammonium salt or cinnamoyl moiety were synthesized and their photosensitive properties as photoinitiator were characterized by UV–vis spectroscopy. The intramolecular electron transfer of SP dyes containing quaternary ammonium salt was much faster and can initiate the photopolymerization under UV irradiation though the photochromic properties than those of SPs containing cinnamoyl group. A photoinitiation system containing SPs and the hexaarylbisimidazoles was studies, and the initiation properties were tested by monitoring the conversion rate of double‐bond at 810 and 1640 cm−1 with ‐time infrared spectroscopy. It was found that the system containing our SP derivatives exhibited much higher initiating efficiency than ever reported SP dyes in the photopolymerization of 2‐phenoxyethylacrylate/N‐vinylcarbazole. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Thermoresponsive Semicrystalline Poly(ε-caprolactone) Networks: Exploiting Cross-linking with Cinnamoyl Moieties to Design Polymers with Tunable Shape Memory

The overall goal of this study was to synthesize semicrystalline poly(ε-caprolactone) (PCL) copolymer networks with stimuli-responsive shape memory behavior. Herein, we investigate the influence of a cinnamoyl moiety to design shape memory polymer networks with tunable transition temperatures. The effect of various copolymer architectures (random or ABA triblock), the molecular weight of the crystalline domains, PCL diol, (M(w) 1250 or 2000 g mol(-1)) and its composition in the triblock (50 or 80 mol %) were also investigated. The polymer microstructures were confirmed by NMR, DSC, WAXS and UV-vis spectroscopic techniques. The thermal and mechanical properties and the cross-linking density of the networks were characterized by DSC, tensile testing and solvent swelling, respectively. Detailed thermomechanical investigations conducted using DMA showed that shape memory behavior was obtained only in the ABA triblock copolymers. The best shape memory fixity, R(f) of ~99% and shape recovery, R(r) of ~99% was obtained when PCL diol with M(w) 2000 g mol(-1) was incorporated in the triblock copolymer at a concentration of 50 mol %. The series of triblock copolymers with PCL at 50 mol % also showed mechanical properties with tunable shape memory transition temperatures, ranging from 54 °C to close to body temperature. Our work establishes a general design concept for inducing a shape memory effect into any semicrystalline polyester network. More specifically, it can be applied to systems which have the highest transition temperature closest to the application temperature. An advantage of our novel copolymers is their ability to be cross-linked with UV radiation without any initiator or chemical cross-linker. Possible applications are envisioned in the area of endovascular treatment of ischemic stroke and cerebrovascular aneurysms, and for femoral stents.

Recent advances in the development of cinnamic-like derivatives as antituberculosis agents

Introduction: The high susceptibility of human immunodeficiency virus-infected people to tuberculosis (TB), the emergence of multi-drug-resistant (MDR-TB) strains and extensively drug-resistant (XDR-TB) ones, has brought TB into the focus of urgent scientific interest. As a result, there has been an upsurge in recent years to find new anti-TB agents, with the cinnamoyl moiety having been identified as a particularly simple and effective pharmacophore for this purpose.Areas covered: This review aims at highlighting the potential of (non)natural cinnamic derivatives to treat TB. It provides an overview of the worldwide recent patent and literature surrounding this type of easy-to-prepare small molecules. There is a special focus on their salient structural and chemical features involved in the reported anti-TB activities.Expert opinion: Cinnamic derivatives clearly appear as attractive drug candidates to combat TB. So far, literature has reported that they are easy to synthesize and have promising anti-TB activities. Nevertheless, the mode(s) of action of these small molecules remain(s) to date obscure, which is why the implicated molecular mechanisms deserve to be investigated in further detail in the near future.

Characterization of hydroxycinnamoyltransferase from rice and its application for biological synthesis of hydroxycinnamoyl glycerols

Hydroxycinnamoyltransferases (HCTs) catalyze the transfer of the cinnamoyl moiety from hydroxycinnamoyl-CoA to various acceptors such as shikimic acid, quinic acid, hydroxylated acid, and glycerol. Four rice HCT homologues (OsHCT1–4) to tobacco HST were cloned, and OsHCT4 was expressed in Escherichia coli as a glutathione S-transferase fusion protein. Using the purified recombinant protein and biotransformation techniques, whether OsHCT4 shows hydroxycinnamoyltransferase activity with a variety of acyl group acceptors was investigated. The results of high performance liquid chromatography (HPLC) and mass spectrometry (MS) established that OsHCT4 mediated the trans-esterification of glycerol as well as shikimic acid in the presence of hydroxycinnamoyl-CoA. The structure of the reaction product was determined using nuclear magnetic resonance spectroscopy (NMR). E. coli cells co-expressing 4CL (4-coumarate:coenzyme A ligase) and OsHCT4 converted p-coumaric acid, ferulic acid, and caffeic acid into the corresponding glycerides. While this conversion is very efficient in vitro, the physiological significant in rice is currently unknown.

Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells

In the present study, we report the design and synthesis of novel analogs of cinnamates, thiocinnamates and thionocinnamates and evaluated the potencies of these analogs to inhibit TNF-α induced ICAM-1 expression on human endothelial cells. By using whole cell-ELISA, our screening data demonstrated that ethyl 3′,4′,5′-trimethoxythionocinnamate (ETMTC) is the most potent inhibitor of TNF-α induced ICAM-1, VCAM-1 and E-selectin. As functional consequences, ETMTC abrogated TNF-α induced adhesion of neutrophils to the endothelial monolayer. Structure–activity relationship studies revealed the critical role of the chain-length of the alkyl group in the alcohol moiety, number of methoxy groups in the aromatic ring of the cinnamoyl moiety and the presence of the α, β- C–C double bond in the thiocinnamates and thionocinnamates.

Photoreaction Behaviors of Two Liquid Crystalline Cinnamoyl Compounds with Different Phase in Solution and Mesomorphic States

A novel nematic liquid crystal compound containing a cinnamoyl moiety (PCPC) and a typically cholesteric liquid crystal cholesteryl cinnamate (CC) were synthesized to explore the mechanism ofcinnamoyl compounds, and the chemical structures of photodimerization were confirmed by Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance spectral analysis. The photoreaction behaviors of these two cinnamoyl compounds in mesomorphic state and solution were investigated, UV-Vis spectral analysis was used to analyze the photoproduct. The results show that the photochemistry of PCPC in nematic state involves both photodimerization and photoisomerization, while CC shows a complex reaction which can be divided into three parts, and this has enabled us to present new data and interpretations regarding the [2+2] photocycloaddition reaction. Additionally, the results of UV-Vis spectral analysis in solutions strongly suggest that UV-Vis spectral analysis can be used to study the kinetic behaviors of cinnamoyl moiety photoreaction.