Study on the Synthesis of Phenylacetic Acid by Carbonylation of Benzyl Chloride under Normal Pressure

The influences of some factors on the yield of phenylacetic acid in thecarbonylation of benzyl chloride were studied in this paper. These factors included the variety andcontent of catalyst, and that of solvent, way of material feeding, reaction temperature, sodiumhydrate concentration, triphenylphosphine content, presence of surfactant, the ratio of organicphase volume to aqueous phase volume etc. The optimum reaction conditions were found to be: with aone-time pour of 0.15 g Pd(PPh_3)_2Cl_2, 0.24 g PPh_3, 75 ml NaOH of 3.5 mol/L, 20 ml benzylchloride and 55 ml n-butyl alcohol, and the reaction was carried out at 50℃ for about 3 hours. Theas-obtained yield of phenylacetic acid was as high as 97.6%. In addition, the influences of thepresence of phenylacetic acid and air in the reaction system were also studied. The results showedthat the presence of air in the system and the entrainment of phenylacetic acid in the circulatingorganic phase had great influence on the reaction rate, the stability and performance of catalystand the yield of phenylacetic acid.

Synthesis, Crystal Structure and Luminescence Property of a Cd(Ⅱ) Complex Assembled by 4-Carboxymethoxy Phenylacetic Acid

A new structure with the molecular formula [CdL]n was formed by CdSO4 with 4-carboxymethoxy phenylacetic acid （H2L） through the hydrothermal method. The complex was characterized by elemental analysis and infrared spectroscopy. The structure of the complex was determined by single-crystal X-ray diffraction, which is of monoclinic system, space group P21/c with a = 10.3887（2）, b = 7.10710（10）, c = 14.7212（2） , β = 120.6940（10）°, V = 934.65（3） 3, Dc = 2.278 g·cm-3, Z = 4, F（000） = 624, S = 1.022, the final R = 0.0187 and wR = 0.0487 for 2000 observer reflections （Ⅰ 〉 2σ（Ⅰ））. The center metal ion Cd（Ⅱ） in the complex is six-coordinated in a distorted octahedral geometry, and is connected with L ligands to form a 3D fishing net structure, which is a novel （3,6） network topology. The luminescence of the complex has been investigated, and the result reveals that it displays luminescent property in the voilet region.

Inhibitory Effects of Phenylacetic Acid on Proliferation of Human Pancreatic Carcinoma BXPC-3 Cells by the Regulation of Adenosine Deaminases Acting on RNA

The effect and mechanism of phenylacetic acid on the proliferation of pancreatic carcinoma cells were investigated in cultured pancreatic carcinoma BXPC-3 cells by means of 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay and flow cytometry assay.The results show that the treatment of pancreatic carcinoma cells with phenylacetic acid significantly inhibited the cell proliferation in time-dependent and dose-dependent manners.The proliferation of BXPC-3 cells was inhibited at the stage of S phase,the cells at the end stage of S phase were accumulated abundantly,and thus DNA synthesis could not be accomplished entirely.In addition,the expression of adenosine deaminases acting on RNA（ADARs） mRNA in BXPC-3 cells and pancreatic carcinoma specimen were detected by RT-PCR.Having been treated with phenylacetic acid,ADAR2 mRNA in BXPC-3 cells was significantly decreased,the differences were of statistical significance（P0.01）.Taken together,these results suggest that phenylacetic acid may likely regulate the proliferation of pancreatic carcinoma cells through the regulation of ADAR2 mRNA expression.

ADSORPTION OF PHENYLACETIC ACID ON MACROPOROUS POLYMERIC ADSORBENTS

Several macroporous polymeric adsorbents (NDA-999, XAD-8, X-5 and XAD-2) were employed in the study to adsorb phenylacetic acid from aqueous solution. Effect of salt and ambient temperature on adsorption was studied using NDA-999 adsorbent and the adsorption process conforms to Freundlich抯 model reasonably. Adsorption dynamics were conducted in batch experiments in order to make clear the mechanism of adsorption process. It is proved that the squared driving force mass transfer model can be adopted to elucidate the process. The treatment process of industrial wastewater containing high strength of phenylacetic acid was proposed for cleaner production of phenylacetic acid.

Bacteroides fragilis Supernatant Extracts Enriched in Phenylacetic Acid Induce a Cytotoxic Effect in Mammalian Cells

Bacteroides species are nearly half of the fecal flora community and some are host symbionts crucial to host nutrition and systemic immunity. Among Bacteroides species B. fragilis strains are considered to be the opportunistic ones, being the most isolated anaerobic bacteria in clinical samples. Cell-free supernatants of 65 B. fragilis strains were assayed and they were capable of inducing vacuolating phenotype on Vero cells lineage. The supernatant of the Bacteroides fragilis ATCC 23745 strain was elicited to have the strongest vacuolating effect on Vero cells monolayers and peritoneal macrophages. Some drastic cell alterations were observed, such as a general disorganization of cytoplasm and chromatin condensation, evidencing cell death. By transmission electron microscopy it was confirmed that the vacuoles observed were, in fact, swollen mitochondria. An immunocytochemical assay, TUNEL, was used to confirm this hypothesis and showed that Vero cells and peritoneal macrophages were dying by apoptotic process after exposition of B. fragilis cell-free supernatant. Physical analysis of the apoptotic factor has revealed properties similar to short-chain fatty acids. After gas chromatography and mass spectrometry analysis, phenylacetic acid (PA) was characterized as the major compound present in the most purified active fraction. We believe that the PA is responsible for the pro-apoptotic effect elicited by the supernatant of B. fragilis cultures.

Electrochemical response of MoS_(2) nanosheets/SiO_(2)-NH_(2) nanoparticles modified glassy carbon electrode to phenylacetic acid

Phenylacetic acid(PAA)is a primary raw material for illegal Methamphetamine(MATM)synthesis under the strong precursor chemicals supervisions of safrole and isosafrole.Therefore,trace detection of PAA at ultra-low concentration is a strategic technique and an urgent issue in the field of drug control.In this paper,trace determination of PAA at sub-nmol-L-1 concentration level is achieved by hydrogen bond adsorption and electrochemical catalysis through the prepared aminated SiO_(2)nanoparticles(SiO_(2)-NH_(2) NPs)and MoS_(2) nanosheets(NSs)modified glassy carbon electrode(GCE).The prepared MoS_(2) NS s/SiO_(2)-NH_(2) NPs modified electrode represents a detecting limit of 0.0989 nmol·L^(-1)and an obvious increasing linear range before the concentration increasement up to 60 nmol·L^(-1)in square wave voltammetry(SWV)responses of PAA.The SWV response of the modified electrode to PAA in the concentration range within 100 nmol·L^(-1)is higher than phenol,acetic acid(HOAc)and benzoic Acid(BEN).This electrochemical method for trace detection of PAA in aqueous solution with desired performance provides a feasible scheme for the detection of other drugs and aromatic precursor chemicals.

Amplification of an MFS Transporter Encoding Gene penT Significantly Stimulates Penicillin Production and Enhances the Sensitivity of Penicillium chrysogenum to Phenylacetic Acid

Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane. Penicillin is historically important as the first discovered drug against bacterial infections in human. Although the penicillin biosyn- thetic pathway and regulatory mechanism have been well studied in Penicillium chrysogenum, the compartmentation and molecular transport of penicillin or its precursors are still poorly understood. In search of the genomic database, more than 830 open reading frames （ORFs） were found to encode transmembrane proteins of P. chrysogenum. In order to investigate their roles on penicillin production, one of them （penT） was selected and cloned. The deduced protein ofpenTbelongs to the major facilitator superfamily （MFS） and contains 12 transmembrane spanning domains （TMS）. During fermentation, the transcription of penT was greatly induced by penicillin precursors phenylacetic acid （PAA） and phenoxyacetic acid （POA）. Knock-down of penT resulted in significant decrease of penicillin production, while over-expression of penT under the promoter of trpC enhanced the penicillin production. Introduction of an additional penT in the wild-type strain of P. chrysogenurn doubled the penicillin production and enhanced the sensitivity of P. chrysogenum to the penicillin precursors PAA or POA. These results indicate that penT stimulates penicillin production probably through enhancing the translocation of penicillin precursors across fungal cellular membrane.

Two new phenolic glycosides from the aerial parts of Androsace umbellata

Two new phenolic glycosides, 2-hydroxy-4-O-β-D-glucopyranosylphenylacetic acid methyl acetate （1） and 2-hydroxy-4-O-β-D- glucopyranosylphenylacetic acid （2） were isolated from the aerial parts ofAndrosace umbellata. Their structures were elucidated by spectral techniques. C 2009 Wen Cai Ye. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Crystal Structure and Characterization of Neodymium Phenylacetate Hydrate

The crystal structure of Nd(ph-CH_2COO)_3H_2O has been determined by X-ray diffraction technique.The crystal behmgs to orthorhombic system with space group P_(na)2_1,cell parameters a=0.7983(1)nm, h=1.3957(1)nm,c=2.0282(2)nm;V=2.2598(15)nm^3,Z=4.The Mechanism and enthalpy changes of thermal decomposition reaction of the title complex have been studied by TG-DTG-DTA and DSC.

THE EFFECT OF PHENYLACETATE ON THE EXPANSION AND CYTOTOXIC ACTIVITY OF ADHERENT LAK CELLS FROM PATIENTS WITH HEPATOCELLULAR CARCINOMA

Objective: To improve the preparation of adherent lymphokine-activated killer (A-LAK) cells and study the synergistic anti-tumor effect of phenylacetate (PA) and A-LAK cells. Methods: A-LAK cells were obtained from peripheral blood mononuclear cells (PBMC) of patients with hepatocellular carcinoma (HCC) by using L-phenylalanine methyl ester (PME) to deplete immunosuppressive monocytes. The proliferation of SMMC7721 cell line treated with PA was studied. A-LAK cells were treated with the supernatant of SMMC7721 cells which had been pretreated with PA and the changes of the proliferation and anti-tumor activity of A-LAK cells were investigated. Results: The expansion of A-LAK cells was significantly higher than that of non-adherent LAK (NA-LAK) cells as well as regular LAK cells. The growth of SMMC7721 cells was significantly suppressed by PA. The supernatant of cultured tumor cells intensively suppressed the proliferation and cytotoxicity of A-LAK cells, but the suppressive effect of supernatant treated with PA previously was decreased. Conclusion: A-LAK cells could be simply prepared by using PME, and showed a synergistic anti-tumor effect with the combination of PA.

Effects of Phenylacetate on Cell Proliferation and Homeobox Genes Expression in the HCT-8 Colorectal Carcinoma Cell Line

To study the effects of phenylacetate （PA） on cell proliferation and homeobox （HOX） genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups （ P1, P2, P3） according to their primer sequences, and the samples of cells were analyzed for the HOX genes＇ mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The level of the HOX genes＇ expression was expressed as the ratio expression rate of HOX gene to the β-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA＊ expression（0. 5781 ±0. 0836） is significantly lower than that of the untreated group （0. 7701 ± 0. 0883 ） in HCT-8 cells （p 〈 0. 001 ）. Both the mRNA expressions of groups P2 （0. 3941 ± 0. 0819） and P3 （0. 5601 ± 0. 0736） in the PA treated group are significantly higher than those of the untreated groups P2（0. 1221±0. 0782） and P3 （0. 1806 ± 0. 0811 ） in HCT-8 cells（p 〈 0. 001）. PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.

Two New Norisoprenoid Derivatives from the Red Alga Gymnogongrus flabelliformis

Two new norisoprenoid derivatives have been isolated from the red alga Gymnogongrus flabelliformis. Their structures were elucidated as （3R, 6R, 7E）-（＋）-3-O-phenylacetyl-4,7-megas- tigmadiene-9-one and （3R,TE）-（-）-3-O-phenylacetyl-5,7-megastigmadiene-9-one, respectively, by spectroscopic methods including HRMS, 1D and 2D NMR techniques.

Increasein the Activity of Human Breast CancerCells to Induce Cytotoxic T Lymphocytes by Sodium Phenylacetate

The effects of differentiation inducer sodium phenylacetate on antigen expression of human breas cancer MDA-453 cells and their activity to induce allospecific cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) were investigated. The results showed that sodium phenylacetate could the expression of HLA-A2 molecules, intercellular adhesion molecule-1 (ICAW-1) and protein HER-2/neu on the surface of MDA-453 cells. In mixed allogenic PBMC/MDA-453 cell (shared the same HLA-A2 locus) culture in vitro, MDA-453 cells could stimulate PBMC growth in the presence of low dose of interleukin-2 (IL-2 ), but sodium phenylacetate-treated MDA-453 cells were more potent for stimulating PBMC growth than the untreated cells. PBMC obtained from frow culture at 7th day could kill MDA-453 cells. The cytotoxicity of PBMC obtained form the culture at 21st day was restricted to MDA-453 cells (PBMC could hardly kill K562 and Raji cells), so the PBMC at this time could be called allospecific CTL. Sodium phenylacetate-treated MDA-453 cells were more potent for inducing allospecific CTL than the untreated cells in mixed allogenic PBMC/MDA-453 cell culture. In summary, sodium phenylacetate could increase the activity of breast cancer MDA-453 cells to induce allospecific CTL with a corresponding effect on antigen expression.

Treatment of Esthesioneuroblastoma and Nonsmall Cell Lung Cancer with Phenylbutyrate

Esthesioneuroblastoma is a malignant tumor, arising in the upper nasal cavity, that could spread to the frontal lobe of the brain as well as metastasize to the lymph nodes. Due to the low incidence of this tumor, FDA-approved treatment modalities do not exist and clinical trials have not been performed. We present an interesting case of a 66-year-old female, diagnosed with Kadish stage B esthesioneuroblastoma and stage IIA nonsmall cell carcinoma of the lung, who benefited from our treatment. Both malignancies were diagnosed in 2002 at which time the patient consented to undergo left upper lobectomy for her lung cancer, but she refused the craniofacial resection and radiation therapy recommended for treatment of her esthesioneuroblastoma. From 2003 to 2004 she received treatment at the Burzynski Clinic with oral sodium phenylbutyrate (0.2 g/kg/day). She tolerated the treatment very well without significant adverse events. Gradual reduction in her tumor size was confirmed by repeat MRIs. From treatment start in March 2003 to December 2003 her tumor decreased by 40%. Subsequent MRI from March 2004 revealed increased tumor size, which, however, was still a 13% reduction from the baseline MRI. What is important to mention is that in addition to shrinkage of the esthesioneuroblastoma, the patient obtained the clinical benefit of 3.5-years longer survival than was predicted for her lung cancer—whereas the median survival for a patient with stage IIA adenocarcinoma of the left upper lobe of the lung is approximately two years, our patient survived more than five and a half years. The effect of phenylbutyrate (PB) and its metabolite phenylacetate on neuroblastoma and lung cancer is documented by numerous preclinical studies and is also evident in this case. It is proposed that the activity of these two compounds is mediated through increased expression of the p21 tumor suppressor gene. p21 is a strong inhibitor of cyclin-D and cyclin-dependent kinase 4, which contribute to undifferentiated phenotype in neuroblastoma and are instrumental in cell cycle progression from G1 to S phase. It is hoped that future research and combination of PB with other chemotherapeutic and targeted agents will provide better control of esthesioneuroblastoma and lung cancer.

Phenylacetylglutaminate and Phenylacetate in Combination Upregulate VDUP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells

Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells;2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells;3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.

Synthesis,Crystal Structure and DFT Calculation of 2-Methoxyimino Phenylacetate Derivatives Containing 1,3,4-Oxadiazole Ring

Four novel 2-methoxyimino phenylacetate derivatives containing 1,3,4-oxadiazole ring were designed and synthesized from the key intermediate of Trifloxystrobin or Azoxystrobin via intermediate derivatization and active structure splicing.The chemical structures of the target compounds were confirmed by]H NMR,13C NMR and elemental analysis.The crystal structure of methyl(E)-2-(methoxyimino)-2-(2-(((5-((4-methoxyphenoxy)methyl)-1,3,4-oxadiazol-2-yl)thio)methyl)phenyl)acetate(Al)was determined by single-crystal X-ray diffraction.Compound A1 belongs to triclinic system,space group Pi with two molecules in each unit cell.The benzene ring plane C(2)-C(3)-C(4)-C(5)-C(6)-C(7)and oxazole ring plane are nearly parallel with the dihedral angle of 6.4°.The benzene ring plane C(12)-C(13)-C(14)-C(15)-C(16)-C(17)and oxazole ring plane are not perpendicular with the dihedral angle of 49.4°.The crystal of compound Al is stabilized by π-π stacking interactions.The fungicidal activities of the target compounds against four plant pathogenic fungi in vitro were tested,and some of them had good activities.The DFT calculation was carried out to study the structure-activity relationship of the title derivatives using Gasian 09 and Multiwfii 3.6.