Cinnamoyl Groups Research Articles

Synthesis of novel cellulose mixesters for transparent responsive films with switchable mechanical properties

Soft actuators have attracted much attention during the last decades due to their potentially broad applications ranging from sensors to artificial muscles. Up to now, most of such soft actuators are still based on synthetic polymers. Herein, we described a novel group of materials derived from sustainable cellulose as potential starting materials for the preparation of soft actuators. To be precisely, cellulose mixesters with acyl esters of distinct chain lengths and cinnamic ester were synthesized through a two-step synthesis and used for the preparation of responsive thin film actuators. These cellulose mixesters have degree of substitution ascribed to stearoyl groups (DSSt) of 1.51 or lauroyl groups (DSLa) of 1.48 and degree of substitution ascribed to cinnamoyl groups (DSCi) around 1.35. Furthermore, the influence of the chain lengths of the two different aliphatic esters as well as the switchable crosslinking of cinnamoyl moieties on the materials properties was further shown. Using these cellulose mixesters, transparent thin films with thickness of 4−15 μm were prepared via facile solvent casting. These films had light-responsive mechanical properties from rigid to elastic after illumination with UV light of distinct wavelengths (254 nm and 310−400 nm). Moreover, the thin films showed shape memory effect and the ability of self-healing.

Preparation and alignment properties of photosensitive polyimide containing benzophenone in main chain

ABSTRACTIn order to study the effect of benzophenone (BP) group in the main chain on the photo-alignment behaviour of cinnamoyl groups, a novel photosensitive polyimide (BTDA-PI-CA) is synthesised by 3,3ʹ,4,4ʹ-benzophenonetetracarboxylic dianhydride (BTDA), 2,2-bis(3-amino-4-hydroxyphenyl)-hexafluoropropane (AHHFP) and cinnamoyl chloride. The BTDA-PI-CA films exhibit good alignment performance after the non-polarised ultraviolet ageing lamp exposure, which is due to the polyimide with BP group can be used to improve the photosensitivity. Moreover, the thermal stability of the LC cells is pretty good and the pretilt angle of the LC cells is 0.5, which can be used in parallel mode LCD.

Synthetic Study of Carthamin: Biomimetic Synthesis of Carthamin Model via Peroxidase‐Catalyzed Oxidative Decarboxylation of Its Precursor Model

A chiral carthamin model (3S,3′S)‐1‐[5‐acetyl‐2,6‐diketo‐3‐C‐β‐d‐glucopyranosylcyclohex‐4‐enylidene]‐1′‐[5′‐acetyl‐3′‐C‐β‐d‐glucopyranosyl‐2′,3′,4′‐trihydroxy‐6′‐oxocyclohexa‐1′,4′‐dienyl]methane, in which two cinnamoyl groups were replaced by an acetyl group, was synthesized by the dimerization of (S)‐2‐acetyl‐4‐C‐(per‐O‐acetyl‐β‐d‐glucopyranosyl)cyclohexadienone with glyoxylic acid, followed by peroxidase‐catalyzed oxidative decarboxylation and de‐O‐acetylation, or de‐O‐acetylation and peroxidase‐catalyzed oxidative decarboxylation. The corresponding total yields were 12.5% or 17.1% from 3‐C‐(per‐O‐acetyl‐β‐d‐glucopyranosyl)phloroacetophenone, and the reaction pathway was identical to the biosynthetic pathway.

Rational Design of Hybrid Natural Products by Utilizing the Promiscuity of an Amide Synthetase

WS9326A and annimycin are produced by Streptomyces asterosporus DSM 41452. WS9326A is a nonribosomal peptide synthetase-(NRPS-) derived depsipeptide containing a cinnamoyl moiety, while annimycin is a linear polyketide bearing a 2-amino-3-hydroxycyclopent-2-enone (C5N) group. Both gene clusters have been sequenced and annotated. In this study, we show that the amide synthetase Ann1, responsible for attaching the C5N unit during annimycin biosynthesis, has the ability to catalyze fortuitous side reactions to polyenoic acids in addition to its main reaction. Novel compounds were generated by feeding experiments and in vitro studies. We also rationally designed a hybrid natural product consisting of the cinnamoyl moiety of WS9326A and the C5N moiety of annimycin by creating a mutant of S. asterosporus that retains genes encoding biosynthesis of the C5N unit of annimycin and the cinnamoyl group of WS9326A. The promiscuity of Ann1 also proved useful for trapping compounds that arise from acyl-ACP intermediates, which occur in the biosynthesis of the cinnamoyl moiety of WS9326A, by hydrolysis. In this pathway, we postulate that sas27 and sas28 genes are involved in the biosynthesis of the cinnamoyl moiety in WS9326A.

Hydroxamic Acid-Based Histone Deacetylase (HDAC) Inhibitors Bearing a Pyrazole Scaffold and a Cinnamoyl Linker

Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, recent studies have demonstrated that epigenetic mechanisms are also implicated in the insurgence and development of cancer. Patterns of the epigenetic component include DNA methylation and histone modifications. Acetylation of histones is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalance of these two enzymatic systems is known to be a key factor in tumor progression. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors (HDACIs) are being investigated to act as cancer chemotherapeutics. Herein, we report the synthesis, docking studies and biological activity of a series of hydroxamic acid-based HDACIs bearing an N1-aryl or N1-H pyrazole nucleus as surface recognition motif and a cinnamoyl group as a linker to the hydroxamic acid zinc-binding group (ZBG). Some of the tested compounds exhibited inhibitory properties towards HDACs and antiproliferative activity against neuroblastoma SH-SY5Y tumor cell line both at micromolar concentrations.

Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer Single-Chain Nanoparticles Prepared through Intrachain Photo-cross-linking.

We report the use of intramolecular cross-linking chemistry as a tool to control the self-assembly of amphiphilic diblock copolymers (di-BCPs). Two amphiphilic di-BCPs of poly( N, N'-dimethylacrylamide)- block-polystyrene (PDMA- b-PS) with photo-cross-linkable cinnamoyl groups in either hydrophobic or hydrophilic blocks were prepared using reversible addition-fragmentation chain transfer polymerization. Intramolecular photo-cross-linking of cinnamoyl groups led to the formation of tadpole-shaped polymer single-chain nanoparticles (SCNPs) consisting of a self-collapsed block as the "head" and an un-cross-linked block as the "tail". When intramolecular photo-cross-linking was carried out in hydrophobic PS blocks, a clear morphological transition from branched cylindrical micelles (for the linear di-BCP) to completely spherical micelles at a dimerization degree of ∼63% was observed. A pattern of morphological transitions from cylindrical micelles to spherical micelles is observed through stepwise downsizing the length of cylindrical micelles when increasing the self-collapse degree of PS blocks, whereas, in case of photo-cross-linking carried out in hydrophilic PDMA blocks, the size of micelles showed a dramatic increase due to the shift of hydrophobic-to-hydrophilic balance. When the cross-linking degree of PDMA blocks reached >60%, tadpole-shaped SCNPs assembled into nonconventional aggregates with a nonsmooth surface. Our results illustrate the impact of chain topologies on the self-assembly outcomes of amphiphilic di-BCPs, which likely opens a door to control the micellar morphologies from just one parent linear di-BCP, rather than resynthesizing BPCs with different volume fractions of the two blocks.

Lignans from the Twigs of Litsea cubeba and Their Bioactivities.

Litsea cubeba, an important medicinal plant, is widely used as a traditional Chinese medicine and spice. Using cytotoxicity-guided fractionation, nine new lignans 1–9 and ten known analogues 10–19 were obtained from the EtOH extract of the twigs of L. cubeba. Their structures were assigned by extensive 1D- and 2D-NMR experiments, and the absolute configurations were resolved by specific rotation and a combination of experimental and theoretically calculated electronic circular dichroism (ECD) spectra. In the cytotoxicity assay, 7′,9-epoxylignans with feruloyl or cinnamoyl groups (compounds 7–9, 13 and 14) were selectively cytotoxic against NCI-H1650 cell line, while the dibenzylbutyrolactone lignans 17–19 exerted cytotoxicities against HCT-116 and A2780 cell lines. The results highlighted the structure-activity relationship importance of a feruloyl or a cinnamoyl moiety at C-9′ or/and C-7 ketone in 7′,9-epoxylignans. Furthermore, compound 11 was moderate active toward protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 13.5 μM, and compounds 4–6, 11 and 12 displayed inhibitory activity against LPS-induced NO production in RAW264.7 macrophages, with IC50 values of 46.8, 50.1, 58.6, 47.5, and 66.5 μM, respectively.

A novel cross-linkable, polyaspartamide derivative-containing cinnamoyl groups with temperature and pH dual stimuli-responsiveness

A novel cross-linkable polyaspartamide derivative-containing cinnamoyl pendant groups, P(HPA-Az)-CA, was designed and synthesized in this study. Chemical structures of the obtained polymers were confirmed by FTIR, UV, and 1H NMR techniques. The transmittance measurement results showed that the prepared polymer P(HPA-Az)-CA displayed temperature and pH dual stimuli-responsive behaviors. The cloud point of P(HPA-Az)-CA could be tuned just by adjusting the introduced percentage of hydrophobic moieties or the pH of polymer aqueous solution. The effect of pH on the cloud point of P(HPA-Az)-CA was investigated by zeta potential, and the results showed that it may be related to the weakened electrostatic repulsion caused by decreased zeta potential with pH decreasing. Diamines (ethylenediamine or cystamine) were adopted to prepare cross-linked micelles using the mixture of P(HPA-Az)-CA aqueous solution and diamines just by one-step heating method. The cross-linked micelles were stable, even when the environmental temperature was below the cloud point of P(HPA-Az)-CA. The cross-linking mechanism between the diamines and α,β-unsaturated carbonyl moieties of P(HPA-Az)-CA was confirmed by 1H NMR. In addition, the micelles cross-linked with cystamine could be disrupted in the presence of 10 mM glutathione. According to the results, the obtained polyaspartamide derivative P(HPA-Az)-CA may be a potential for facilitating drug loading.

Polymeric fibers and microporous films by photo‐crosslinking of triphenylene‐derived liquid crystals

ABSTRACTTwo series of photoreactive discotic liquid crystals consisting of a triphenylene core and six cinnamate units with one (TPC1 n) or two (TPC2 n) n‐alkoxy groups (C nH2n+1O; n = 10–14), respectively, as peripheral groups are synthesized. Both of them are polymerized into fibers up to 2 mm long by UV irradiation in liquid paraffin in the columnar LC temperature ranges. The fiber structures seem to be preconstructed in liquid paraffin. In addition, TPC2 n are shown to form microporous films up to 15 μm in diameter by simply casting the solutions of some solvents followed by drying for several minutes in air at room temperature. Photoirradiation of the films in the LC temperature range converts them to polymeric ones while preserving the microporous and hexagonally ordered structure. From comparison with TPC1 n and the hydrogenated derivative of TPC2 12, the porous film‐forming property is suggested to result from the combination of the double bond of the cinnamoyl group and the two long alkoxy chains on the phenyl ring. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 605–612

Polymer Side-Chain Conjugates를 위한 전구체인 Polydiacetone Acrylamide

Polydiacetone acrylamide (PDAAM), a reactive polymer containing pendant ketone groups was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Kinetic studies indicated a well-controlled behavior of this RAFT polymerization. The characteristics of this RAFT polymerization was also confirmed by a wellcontrolled chain-extending RAFT polymerization using the above-synthesized PDAAM as a macromolecular chain transfer agent. Acid-catalyzed ketalization of PDAAM with trimethylol propane (TMP) was carried out to obtain the polymer containing pendant cyclic ketal groups and hydroxyl groups, PDAAM-TMP. PCL was grafted from PDAAM-TMP by ring-opening polymerization (ROP) in the presence of tin 2-ethylhexanoate as a catalyst to obtain graft copolymer. Basecatalyzed aldol condensation of PDAAM with benzaldehyde was also used to obtain poly[N-(1,1-dimethyl-3-oxo-5-phenyl-pent-4-enyl)-acrylamide] (PDMOPPEAM) having cinnamoyl groups, and the photoreactivity of polymer with cinnamoyl group was studied by UV-visible and IR absorption spectroscopy. Both of these two polymers prepared from PDAAM were characterized by FTIR and 1H NMR spectroscopy. PDAAM can be a multifunctional platform that can undergo further polymerization by ketalization and aldol condensation.

Suspension stability control using light-sensitive polymers

In this paper a novel approach to the flocculation phenomenon was investigated, i.e. application of light-sensitive polymers. A hypothesis was proposed that the energy delivered by an electromagnetic wave will trigger the photo-dimerization reaction, which in turn will lead to the destabilization process via bridging phenomenon. In research two polymers differing in content of light-sensitive component, i.e. cinnamoyl groups, were synthesized by means of conventional free radical copolymerization and postreaction. In the flocculation experiments a model suspension of CaCO3 precipitate in deionized water was used. The experiments were performed using two different mixer configurations. Unfortunately, the postulated mechanism was proved to be wrong. Although both polymers acted as good destabilization agents directly after injection to suspension, the UV radiation had no impact on the process.

CH activations in aldehydes in reactions with Ru5(μ5-C)(CO)15

The reaction of Ru5(μ5-C)(CO)15, 1 with benzaldehyde yielded two new pentaruthenium carbido cluster compounds: Ru5(μ5-C)(CO)14[η2-O=C(H)C6H4](μ-H), 2 and Ru5(μ5-C)(CO)14(μ-η2-O=CPh)(μ-H), 3 containing open Ru5C cluster complexes formed by the activation of two different C-H bonds of the benzaldehyde molecule. Compound 2 contains a chelating, ortho-metallated benzaldehyde ligand coordinated to an open Ru5C cluster that is coordinated by the aldehyde oxygen atom and one of the ortho-positioned carbon atoms of the phenyl ring that was formed by loss of a CO ligand and an oxidative addition of the ortho-C-H bond of the phenyl ring to the metal atom. Compound 3 is an isomer of 2 that contains an O=C-coordinated, η2-bridging benzoyl ligand across the open edge of the Ru5C cluster formed by C-H activation at the aldehyde formyl group. The reaction of 1 with trans-cinnamaldehyde yielded two complexes: Ru5(μ5-C)(CO)14[η2-O=C(H)CH=CPh](μ-H), 4 and Ru5(μ5-C)(CO)14[μ-η2-O=CC(H) = C(H)Ph](μ-H), 5. Compound 4 contains an open Ru5 cluster with a chelating cinnamoyl ligand formed by coordination of the aldehyde oxygen atom and the β–carbon atom of the alkene double bond formed by a C-H activation at the alkene atom. Compound 5 contains a η2-bridging, O=C coordinated cinnamoyl group formed by C-H activation at the aldehyde formyl group. The reactions of 1 with furfural and 5-hydroxymethylfurfural yielded similar complexes: Ru5(μ5-C)(CO)14(μ-η2-O=CC4OH3)(μ-H), 6 and Ru5(μ5-C)(CO)14[μ-η2-O=CC4OH2(CH2OH)](μ-H), 7, respectively with each one containing bridging, O=C coordinated acyl ligand formed by C-H activation at the aldehyde formyl group. All of the new compounds were characterized by single-crystal X-ray diffraction analyses.

Fabrication of Nanostructures Composed of Tetrathiafuluvalene Derivatives with Various Side Chains

Design of molecules for specific functions and their structural control in a nanoscale have attracted much interest for device downsizing as well as development of complex and multi-functional devices. In order to obtain nanostructures in various dimensions, supramolecular approaches are quite useful because of the structural flexibility. Furthermore, appropriate design of the constituent molecules may amplify and/or combine their specific functions in the supramolecular systems by proper molecular orientation and intermolecular interaction. Tetrathiafulvalene (TTF) is a strong electron donor, and its complexes with various kinds of electron acceptors are known to become semiconductors, metals and superconductors. In our previous studies, we found that introduction of appropriate substituents with a hydrogen-bonding group to the TTF moiety resulted in formation of its one-dimensional (1D) stacks to form nanofibers. Charge-transfer (CT) complexes of the TTF derivatives were also found to form 1D structures, which was considered as conducting nanowires useful for molecular electronics. In addition, if we can control reversible conformational changes of the molecules in nanowires by external stimuli such as light, electric or magnetic field and heat, the induced motions can be applied for molecular machines as well as switching devices. In this study, we synthesized the TTF derivatives having various side chains as shown in Figure 1A and their self-organization was investigated. Also, the CT complexes were prepared by mixing the TTF derivatives with various acceptor molecules and their electrical properties were evaluated. Characteristics of the mono-TTF compounds 1a–1d are as follows. For all compounds, π-π interaction between TTF moieties is expected. In addition, 1b–1d have phenyl rings which also induce π-π interactions between them. For 1c, cinnamoyl groups in adjacent molecules can react to form a cyclobutane ring by UV irradiation, and this reaction may be useful to fix the supramolecular structures. Amide groups for intermolecular hydrogen-bonding in 1b and 1d are also important to form molecular stacking arrays. Chiral centers in these compounds were introduced for the helical structure formation. The terminal ferrocene moiety in 1d is electrochemically active species, which can be utilized as a stimulus-responsive part. The CT complexes were prepared by mixing the TTF derivatives and F2TCNQ or F4TCNQ. In any combinations, new absorption bands were observed between 600 and 900 nm, suggesting formation of the CT complexes. The nanostructures of the TTF derivatives and their CT complexes were prepared by casting the corresponding toluene solution on HOPG substrates. Although 1b formed nanofibers, 1a, 1c and 1d became amorphous films or nanodots. Among these three compounds, 1a and 1c do not have relatively strong interactions like hydrogen bonding in their substituents. This indicates that the π-π interaction between TTF moieties is not enough to form the 1D nanostructure in general. In the case of 1d with amide groups, the bulky ferrocene groups at the end of the substituents seems to weaken the intermolecular hydrogen bonding, and the 1D nanostructure was not fabricated. Therefore, in order to intensify the π-π interaction of the core part, we synthesized compounds 2a–2d in which TTF units are dimerized with a disulfide bond. The crystallinity of 2a–2d was improved in comparison with the corresponding mono-TTF compounds. By SEM observation, it was confirmed that 2a and 2d formed nanoribbons having the width of about 800 nm and nanofibers having the width of about 200 nm, respectively (Figure 1B). This result suggested that intermolecular interaction was enhanced by the dimerized TTF structure with stronger π-π stacking. Thus, nanofiber formation became possible even in the compound with bulky substituents. In addition, the CT complexes of 2a–2d with F2TCNQ or F4TCNQ were prepared and their nanostructures were observed. Except for the CT complex using 2c, we confirmed the nanofiber formation. All of the CT complexes were found to show conductivity at the semiconductor level of 10-2–10-3 S m-1. Figure 1

Morphology control of shell-crosslinked polymer particles prepared by photo-induced shell-selective crosslinking approach via dispersed state control

HypothesisMorphology control of polymer particles is of great importance for creating functional particulate materials. Photoinduced shell-selective crosslinking approach with spherical polymer particles has been previously developed in a dispersed state, in which the polymer particles could rotate freely, yielding hollow polymer particles after removal of non-crosslinked polymers because photoinduced crosslinking occurred for the entire particle surface. This insight prompted the question of whether non-spherical particles can be obtained if particle rotation is restricted and photoirradiation occurs for only part of the shell region. ExperimentsHerein, we developed a facile approach for morphology control of polymer particles prepared by photoinduced shell-selective crosslinking of spherical polymer particles bearing photoreactive cinnamoyl groups by regulating the dispersed state. The morphology of the polymer particles obtained from the photo-induced shell-selective crosslinking approach in dispersed or non-dispersed states was confirmed. In-situ real time observation of forming the non-spherical polymer particles was also performed by optical microscope. FindingsHollow and bowl-shaped polymer particles were successfully obtained from same spherical polymer particles bearing photo-crosslinking groups in dispersed and non-dispersed states, respectively. The versatility of the approach was confirmed by using various comonomers. Furthermore, post-functionalization for the polymer particles was also successfully performed using functional groups derived from the comonomers.

Reversibly photo-crosslinkable aliphatic polycarbonates functionalized with coumarin

Cinnamoyl and coumarin groups can be used to introduce photo-responsive behaviour to polymer systems, but they have never been directly compared within the same polymer system. Thus, this study examined cinnamoyl and coumarin functionalized aliphatic polycarbonate copolymers to determine their relative suitability for use as biomaterials. Coumarin functionalized polycarbonates photo-crosslinked significantly faster and resulted in networks with high crosslink density when irradiated with UVA radiation. Real-time tracking using rheometry showed that increasing the degree of coumarin functionalization on the aliphatic polycarbonate copolymers resulted in quicker gelation and higher final storage modulus. In addition, decreasing the UV intensity and increasing the sample thickness also increased the final storage modulus. Although no appreciable reversibility was detected for solvent-free or solvent-swelled crosslinked polymer networks, rapid reversibility upon exposure to 254 nm light was observed in dilute solutions. The kinetics of photo-dimerization were third order while the photo-cleavage reaction kinetics were second order with respect to the concentration of the photoactive group. Overall, the photo-reversible crosslinking of coumarin functionalized aliphatic polycarbonates was demonstrated. These polymers have potential for use in photo-crosslinking or photo-reversible biomaterials applications.

Absolute Structures of Wedelolide Derivatives and Structure-Activity Relationships of Protein Tyrosine Phosphatase 1B Inhibitory ent-Kaurene Diterpenes from Aerial Parts of Wedelia spp. Collected in Indonesia and Japan.

Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.

Multifunctional Vesicles from a Self-assembled Cluster-Containing Diblock Copolymer.

We describe a new diblock copolymer composed of two segments with complementary functionalities. One block contains pendent photo-cross-linkable cinnamoyl groups, and the other contains molecular clusters, Co6Se8, capable of multielectron redox processes. This multifunctional macromolecule is synthesized by sequential ring-opening metathesis polymerization of monomers constructed using norbornene moieties. Remarkably, the tethered molecular cluster gives access to three different charge states in N, N-dimethylformamide: neutral, +1, and +2. In tetrahydrofuran, by contrast, the charged copolymer self-assembles into vesicles that inhibit the redox reactions. The wall of these vesicles can be cross-linked by exploiting the photoinduced 2 + 2 cycloaddition of the cinnamoyls to form cyclobutane dimers. Moreover, these vesicles can be loaded with molecular cargo and used as cross-linkable containers; we demonstrate this feature by encapsulating the molecular dye methylene blue into the capsules. Our work is the first report of a well-defined block copolymer containing a metal chalcogenide molecular cluster; more generally, it opens the door to new applications of metal-containing polymers.

Gas-phase domino cyclization of phosphonium ylides leading to the total synthesis of Eustifoline D

Six stabilised phosphonium ylides bearing ortho-benzylaminophenyl and cinnamoyl (or a heterocyclic analogue) groups have been prepared and upon flash vacuum pyrolysis at 800°C were found to undergo cascade cyclization processes to give mainly 3-styrylquinolines but also in some cases ring-fused carbazoles and other fused-ring heterocyclic products. By starting with an appropriate ring-methylated precursor the natural product Eustifoline D was obtained in 19% yield in the pyrolysis in addition to the 3-(2-furylethenyl)quinoline (46%).

Fabrication of Redox-Responsive Degradable Capsule Particles by a Shell-Selective Photoinduced Cross-Linking Approach from Spherical Polymer Particles.

In this study, a fabrication route towards functional capsule particles was successfully developed by means of a self-templating shell-selective cross-linking strategy that enables us to prepare shell-cross-linked hollow polymer particles directly from homogeneous spherical polymer particles. To prepare redox-responsive degradable capsule particles, a newly designed monomer bearing a photoinduced post-cross-linking group (cinnamoyl group) and a redox-environment-responsive cleavable group (disulfide group), N-cinnamoyl-N'-methyacryloylcystamine (MCC), was synthesized. Redox-responsive degradable capsule particles were successfully prepared from homogeneous spherical poly(MCC)-based particles by a self-templating shell-selective photoinduced cross-linking approach. Moreover, the cargo loading capability of the shell-cross-linked hollow particles was confirmed through a solvent exchange procedure using dyes, polymer precursors and anticancer reagents. Furthermore, redox-responsive degradability of the capsule polymer particles was also confirmed by adding a reducing agent for cleavage of the disulfide linkage. We hope that the efficient fabrication route of functional capsule particles directly from spherical polymer particles opens efficient routes for the fabrication of a wide range of capsule particles; in particular, this technique is robust, productive, and facile because neither additional sacrificial template particles nor toxic solvents are required.

Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents

Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.