Condensation reaction of β-triphenylgermanyl propionic acid with α-hydroxy phosphonic ester and the structure of the products

<正> The sterically hindered condensation of β-triphenylgermanyl propionic acid withα-hydroxy phosphonic ester has been studied.The failure of conventional ways of the condensation is probablydue to the bulky groups Ph3Ge-and-P（O）（OR）2.However,several novel O,O-dialkyl-α-（β-triphenylgermanyl）propionoxy phosphonic esters have been synthesized successfully in good yields by using DCC catalyzed bypyridine or HOBt.The reactivity has much to do with the steric hindrance of the groups R.Thelarger the OR,the slower the reaction rate is.All the new products were characterized by1H NMR,IRspectra,MS and elemental analyses.A single crystal A1was obtained and the structure was determined byX-ray diffraction.Preliminary bioassays showed that the new products exhibit antitumor activity.

响应面法优化P.acidipropionici产酸发酵培养基

利用响应面分析法优化产酸丙酸杆菌发酵产酸培养基。在单因素试验的基础上,采用Box-Behnken试验设计,选定甘油、混合氮源(酵母提取物:胰酶大豆肉汤=2:1)和磷酸氢二钾3个关键因子为响应因子,以丙酸产量为响应值建立多元二次回归方程,在分析各个因素的显著性和交互作用后,确定了产酸丙酸杆菌发酵产酸的最优培养基为:甘油44.4g/L、混合氮源(酵母提取物:胰酶大豆肉汤=2∶1)27.0g/L、K2HPO42.0g/L,丙酸产量最大预测值为20.75g/L。经过优化,丙酸产量提高了151%,实验值与预测值基本相符。

Effect of lactic acid bacteria and propionic acid on conservation characteristics,aerobic stability and in vitro gas production kinetics and digestibility of whole-crop corn based total mixed ration silage

This study was conducted to evaluate the effect of lactic acid bacteria and propionic acid on the fermentation quality, aer- obic stability and in vitro gas production kinetics and digestibility of whole-crop corn based totalmixed ration （TMR） silage. Total mixed ration was ensiled with four treatments： （1） no additives （control）; （2） an inoculant （Lactobacillus plantarum） （L）; （3） propionicacid （P）; （4） propionic acid＋lactic acid bacteria （PL）. All treatments were ensiled in laboratory-scale silos for 45 days, and then subjected to an aerobic stability test for12 days. Further, four TMR silages were incubated in vitro with buffered rumen fluid to study in vitro gas production kinetics and digestibility. The results indicated that all TMR silages had good fermentation characteristics with low pH （〈3.80） and ammonia nitrogen （NH3-N） contents, and high lactic acid contents as well as Flieg points. Addition of L further improved TMR silage quality with more lactic acid production. Addition of P and PL decreased lactic acid and NH3-N contents of TMR silage compared to the control （P〈0.05）. After 12 days aerobic exposure, P and PL silages remained stable, but L and the control silages deteriorated as indicated by a reduction in lactic acid and an increase in pH, and numbers of yeast. Compared to the control, addition of L had no effects on TMR silage in terms of 72 h cumulative gas production, in vitro dry matter digestibility, metabolizable energy, net energy for lactation and short chain fatty acids, whereas addition of PL significantly （P〈0.05） increased them. L silage had higher （P〈0.05） in vitro neutral detergent fiber digestibility than the control silage. The results of our study suggested that TMR silage prepared with whole-crop corn can be well preserved with or without additives. Furthermore, the findings of this study suggested that propionic acid is compatible with lactic acid bacteria inoculants, and when used together, although they reduced lactic acid production of TMR silage, they improved aerobic stability and in vitro nutrients digestibility of TMR silage.

Synthesis and Crystal Structure of 2-[(2-Chloropyridin-4-yl)oxy]-3,3-diphenyl-3-methoxypropionic Acid

The title compound was synthesized and its crystal structure was determined by single-crystal X-ray diffraction.The crystal is of orthorhombic system（C21H18ClNO4,Mr = 383.81）,space group Pca21 with a = 13.913（3）,b = 10.273（2）,c = 26.488（5）,V = 3786.1（13） 3,Z = 8,Dc = 1.347 g/cm3,F（000） = 1600,μ = 0.228 mm-1,the final R = 0.0550 and wR = 0.1278 for 5065 observed reflections（I 2σ（I））.The title compound in a racemic form was found to exist as a mixture of two enantiomers in an equal ratio in the unit cell.The intermolecular hydrogen bonds link the molecules in a head-to-end manner to generate an infinite chain.

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for autism.Mitochondrial dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine monophosphate.Rat models of autism were established by intracerebroventricular injection of propionic acid.These rat models had memory dysfunction,decreased muscle coordination and gait imbalance.Biochemical estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid biomarkers.Oral administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent manner.These findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with autism.This study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval No.RITS/IAEC/2014/03/03).

Optimization of Propionic Acid Feeding for Production of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in Fed-Batch Culture of Ralstonia eutropha

The feeding method of propionic acid for production ofpoly(3-hydroxybutyrate-co-3-hydro xyvalerate) [P(3HB-co-3HV)] by fed-batch culture of Ralstoniaeutropha was optimized to achieve high cell density and high 3HV yield. Effects of different feedingstrategies of propionic acid on the production of P(3HB-co-3HV) were investigated. A decline ofspecific synthesis rate of copolymer and the yield of 3HV unit from propionic acid were observed dueto the propionic acid accumulation in culture broth when the feeding solution with highP/G(propionic acid to glucose) ratio was employed. It was further confirmed by controlling propionicacid concentration at a low level in the separate feeding of propionic acid. An optimal feedingstrategy was demonstrated to reduce the propionic acid accumulation. The cell concentration,P(3HB-co-3HV) productivity and 3HV unit fraction reached to 163.9kg·m^(-3), 1.8kg·m^(-3)·h^(-1),and 10.6%(by mass), respectively, resulting in a yield of 0.33g HV per g propionic acid.

An efficient route towards R-2-phenoxypropionic acid synthesis for biotransformative production of R-2-(4-hydroxyphenoxy)propionic acid

R2(4hydroxyphenoxy)propionic acid(RHPPA)is a key intermediate for the synthesis of classic herbicides with high selectivity against grassy weed.The main route for RHPPA biosynthesis is to hydroxylate the substrate R2phenoxypropionic acid(RPPA)at C4 position with microbes.In order to provide sufficient RPPA for the industrial production of RHPPA,an effective RPPA synthesis method was established and optimized in this work.The synthesis process mainly consisted of two steps:(1)synthesis of S2chloropropionic acid from Lalanine via diazotization and chlorination reactions;and(2)synthesis of RPPA from S2chloropropionic acid and phenol via etherification reaction.The optimal reaction conditions were as follows:HCl:NaNO_(2):KI:LAla=2.0:1.2:0.7:1.0(in molar),125℃reflux for 1.5 h,with KI as catalyst,and KI:S2chloropropionic acid:phenol=0.075:1.2:1.0(in molar).Under these conditions,an improved molar conversion rate(74.9%,calculated in phenol)was achieved.After extraction using anionic exchange resin Amberlite IRA400(CI),RPPA product with a purity of 95.08%was obtained.The purified RPPA was identified and evaluated in the application of the biotransformative production of RHPPA.The results indicated that the synthesized RPPA supported the RHPPA biosynthesis with a comparable yield as that of the standard RPPA.The RPPA synthesis method provided herein exhibited the advantages of low price and easy availability of raw materials,less toxicity of reagents,simple manipulations,and low equipment/instrument requirements.

HPLC Determination of Neurotoxin β-N-oxalyl-L-α, β-diaminopropionic acid and Its α -Isomer in Lathyrus sativus by Precolumn Derivatisation with 1-Fluoro-2,4-dinitrobenzcne

A rapid and simple method is presented for determining β-N-oxalyl-α. β- diaminopropionic acid (β -ODAP) and its much less toxic α -isomer (α -ODAP) in Lathyrus sativus. Seed and foliage extracts of Lathyrus sativus were treated with 1-fluoro-2,4-dinitrobenzene (FDNB) and a reversed-phase high-performance liquid chromatographic method for the separation of the derivatives in the pmol range is reported.

Salt Effect on the Liquid-Liquid Equilibrium of （Water ＋ Propionic Acid ＋ Cyclohexanol） System at T=（298.2,303.2,and 308.2） K

Effects of salt and temperature on the liquid phase equilibrium of the(water + propionic acid + cyclohexanol) system were investigated.The liquid-liquid equilibrium data in the presence of KCl for various salt ionic strength of 0.5,1.0,1.5,2.0,and 2.5 mol·dm3 and in absence of the salt at T=(298.2,303.2,and 308.2)K were determined.The experimental results were correlated based on the Othmer-Tobias equation and Pitzer ion-interaction model.Thermodynamic properties such as distribution coefficients and activity coefficients of propionic acid in water + cyclohexanol were determined.In addition,the separation factor,S,of the chosen solvent was obtained for the investigated system.

Enantioselective esterification of(R,S)-2-(4-methylphenyl)propionic acid via Novozym 435:Optimization and application

This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lipases.Of the alcohols screened,n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane.Response surface methodology(RSM)was used to evaluate the influence of the factors,such as temperature,enzyme amount,substrate concentration and reaction time on the substrate conversion(c)and enantiomeric excess(ee).The correlation coefficient R2 for enantiomeric excess and the conversion are 0.9827 and 0.9910,respectively,indicating that can accurately predict the experimental results.By simulation and optimization,the optimal conditions were obtained,involving 600 mmol·L^-1 MPPA concentration(0.60 mmol),850 mmol·L^-1 hexanol concentration(0.85 mmol),58 mg enzyme amount,75℃temperature and 4.5 h reaction time,respectively.Under the optimized conditions,the experimental values of conversion and enantiomeric excess were 89.34%and 97.84%,respectively,which are in good agreement with the model predictions.

Mild stir-assisted membrane dispersion for enhancing propionic acid extraction

Mild stir-assisted membrane dispersion extraction(MDE) method was employed to enhance propionic acid(HA)extraction and compared to the mechanical stirred extraction(MSE) method. Triocylamine(TOA) and tributyl phosphate(TBP) were chosen as model extractant to extract HA. Firstly, droplet size and the size distribution of organic phase were analyzed, and then the effects of phase ratio, extractant and HA concentration on extraction performance were investigated. Comparing the two extraction methods, the results show mild stir-assisted MDE method reduced the mass transfer equilibrium time compared to MSE method. The mass transfer mechanism was explored by analyzing mass transfer resistance. Mild stir-assisted MDE had less total mass transfer resistance than MSE. When the extractant concentration was 40%, the extraction process was controlled by organic phase mass transfer process with HA volume fraction was 1% and controlled by both of reaction process and organic phase mass transfer process when HA concentration increased to 5%. This work may provide a new type of extraction method for the recovery of organic carboxylic acid.

Synthesis of Optical Active 2-Arylpropionic Acids

(S)-2-(6'-methoxyl alpha:-naphthyl) propionic acid ((S) Naproxen,: ee 99%) has been prepared starting from (6-methoxyl-alpha -naphthyl)propan-1-one and D-Sorbitol under SmCl3 catalysis.

Basic fibroblast growth factor increases the numbe of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice

This study aimed to investigate the number of amino methyl isoxazole propionic acid （AMPA） receptors and production of endogenous neural stem cells in the SOD1 G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor （FGF-2）. A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice.

Synthesis and Crystal Structure of O,O-Dimethyl-N-(β-triphenylgermanyl)propionyl-α- aminobenzylphosphonates

The title compound (C30H32NO4PGe), O,O-dimethyl-N-(β-triphenylgermanyl) propionyl-α-aminobenzylphosphonates was synthesized by a convenient method, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal is triclinic, space group P-1 with parameters: a=9.7753(5), b=11.5773(5), c=13.5059(6) ?, α=104.185(1),β= 95.971(1), γ =96.727(1)°, V=1457.63(12) ?3, Z=2, Mr=574.13, Dc=1.308 g/cm3, λ=0.71073 ?, μ = 1.139mm-1, and F(000)=596. The structure was solved by direct methods. The structure was refined to R=0.0257, wR=0.0705 for 5080 observed reflections with I >2σ(I).The result of structure analysis indicates that atom Ge is sp3 hydridized because the arrangement of the four carbon atoms bonded to it is a distorted tetrahedron. The geometry of the three phenyl groups linking with the Ge atom looks like a propeller form.

Effect of Temperature on the Reaction of 2-(N-acetylamine)-3-(3,5-di-<i>tert</i>-butyl-4-hydroxyphenyl)-propionic Acid with Oxygen in an Alkaline Condition

Results of oxidation 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid oxygen depend on temperature. At 55℃?- 60℃, 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa is formed. The constitution is based on dates of spectrums 1Н and 13С NMR. At 95℃?- 97℃, mixtures of 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa and of 6,8-di-tert-butyl-3-(N-acetylamine)spiro(4,5)deca-1-oxa-5,8-dien-2,7-dione are produced. Structures are calculated by the method of Hartrii-Foka. Values of enthalpies and of entropies allow to assume dynamic isomerism.

Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease

AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.

In vitro investigation of the effect of dairy propionibacteria on rumen pH,lactic acid and volatile fatty acids

Ruminal acidosis is a prevalent disorder in ruminants such as dairy cows and feedlot beef cattle, caused primarily by the inclusion of a high percentage of readily fermentable concentrates in the diet. The disorder presents as an accumulation of lactic acid, a decrease of pH in the rumen and a subsequent imbalance of the rumen fermentation process with detrimental impacts on the animal＇s health and productivity. Dairy propionibacteria, a group of bacteria characterised by utilization of lactic acid as the favoured carbon source, with propionic acid produced as a by-product, were evaluated in this study as potential direct-fed microbials for use in controlling ruminal acidosis. Acidosis was simulated by introduction of high concentrations of lactic acid into rumen fluid samples and a multi-strain in vitro analysis was conducted, whereby changes in pH and lactic acid metabolism were compared in identical acidified rumen samples, following inoculation with various propionibacteria. This was followed by a study to evaluate the effect of bacterial inoculation dosage on acid metabolism. The results indicated that lactic acid levels in the rumen fluid were significantly reduced, and propionic acid and acetic acid concentrations both significantly increased, following addition of propionibacteria. Significant ＇between strains＇ differences were observed, with Propionibacterium acidopropionici 341, Propionibacterium freudenreichfi CSCC 2207, Propionibacterium jensenfi NCFB 572 and P. jensenii 702 each producing more rapid reduction of lactic acid concentration than P. freudenreich# CSCC 2206, P. acidopropionici ATCC 25562 and Propionibacterium thoenii ATCC 4874. Furthermore, the efficacy of this application was dosage related, with the rates of reduction in lactic acid levels and production of propionic acid, both significantly greater for the higher （10^10 cfu mL-1） compared with lower （10^5 cfu mL-1） dosage inoculation. The results confirmed that the introduction of propionibacteria could promote more rapid reduction of lactic acid levels than would occur without their addition, demonstrating their potential in controlling ruminal acidosis.

Clinical Evaluation of an Oral Electrolyte Solution Formulated Based on Strong Ion Difference (SID) and Using Propionate as the Organic Anion in the Treatment of Neonatal Diarrheic Calves with Strong Ion Acidosis

Background: It is postulated that the concentrations of the major strong ions (Na, K, and Cl) in oral electrolyte solutions play a major role in clinical efficacy of these solutions for rehydration and corrections of metabolic acid base derangements. Objectives: The purpose of this study was to test prospectively the efficacy of an OES (OESexp) formulated based on concentration of strong ion difference (SID) and propionate in a group of calves with naturally occurring neonatal diarrhea and clinically detectable dehydration and acid base abnormalities. Animals: Ten client owned calves of varying breeds, 2 - 22 days old, presented to a veterinary teaching hospital with a history of naturally occurring acute undifferentiated diarrhea, progressive depression and dehydration for treatment. Methods: Clinical and laboratory parameters were measured pre and post two oral electrolyte treatments to assess efficacy of the experimental OES to correct clinical and clinico pathological parameters. For the clinical trial the calves served as their own controls. For control of safety of medication 4 normal calves were force fed 4 L of OESexp and followed over a 24 hour period. Results: All calves had severe diarrhea and metabolic acidosis. The metabolic acidosis observed in the plasma of these calves and reflected by pH, HCO3- SID and base deficit was corrected significantly towards reference ranges (p < 0.05) with two 2 L feedings 12 hours apart. Dehydration was significantly corrected and all calves were discharged 1 - 3 days post admission. Conclusion and Clinical Importance: The use of SID is a valid approach when formulating oral electrolytes solutions for use in calves with acute diarrhea and metabolic derangement. Sodium propionate is valid substitute for commonly used sodium base equivalents in North America in oral electrolyte solutions.

利用聚乙烯醇-海藻酸钙固定化Propionibacterium freudenreichii NX-4制备丙酸

以Propionibacterium freudenreichii NX-4为研究对象,采用聚乙烯醇(PVA)和海藻酸钠互配作为固定化载体,考察了其制备丙酸的最佳固定化条件:ρ(PVA)为10.7 g/L,ρ(海藻酸钠)为1.4 g/L,包埋量16%(质量分数),ρ(硼酸)为50 g/L,固定化时间18 h.经15批次的发酵验证,产量稳定,丙酸平均产量为19.64 g/L(葡萄糖40 g/L).以80 g/L的葡萄糖为C源固定化制备丙酸192 h,丙酸产量达35.4 g/L.

A Study on the Mechanism Regulating Acetate to Propionate Ratio in Rumen Fermentation by Dietary Carbohydrate Type

The research direction of our team is nutrition and physiology of ruminants, including dietary nutrition metabolism and rumen microorganisms. Previous research has shown that ruminal acetate-to-propionate ratio is related to diet utilization efficiency. At present, it is believed that the main factors affecting the ruminal acetate-to-propionate ratio are the degradation rate of the diet and the rumen microbial structure, but the main mechanism is unclear. This study found that the effect of ruminal acetate-to-propionate ratio was not affected by the concentration of the fermentation substrate, but was affected by the structure of the rumen microbiota. We believe that changes in the rumen microflora structure are the main mechanism for regulating the ruminal acetate-to-propionate ratio. This will help people to further understand the rumen physiology, thereby gradually improving feed conversion efficiency and reducing production costs. Abstract: In order to explore the mechanism by which diet regulates the acetate-to-propionate molar ratio (A: P ratio), we compared the effect on rumen fermentation parameters and the microbiome by altering the ratio of dietary concentrates to roughage ratio and calcium pyruvate infusion. The test animals were Laoshan dairy goats, and were fed continuously through an automatic feeder. The test groups were fed a base diet of low concentrates, and intraruminally infused with calcium pyruvate at two concentrations. The infusion concentrations were derived from the difference in the rate of carbohydrate degradation of the high and low concentrate diets, and they were artificially set such that the high concentration infusion group was infused with twice the concentration as the low concentration infusion group. The control groups were fed high concentrate (6:4) and low concentrate (3:7) diets, respectively. The following results were obtained by measuring rumen fermentation parameters and microbial composition: the rumen A: P ratio was significantly lower in the high-concentrate diet group than in the low concentrate diet group (P < 0.05). Infusion of low concentration calcium pyruvate had no significant effect on rumen A: P ratio (P > 0.05), while infusion of high concentration calcium pyruvate significantly increased the rumen A: P ratio (P < 0.05). Relative to goats fed the low concentrate diet, those fed the high concentrate diet had a greater abundance of microbes related to propionate production and a reduced abundance of microbes related to fiber degradation. Infusion of pyruvate had no significant effect on rumen microbial structure. The above results indicate that increasing the concentration of the fermentation substrate without affecting the composition of the microflora does not reduce the A: P ratio. Microbiological results showed that the A: P ratio was more closely related to the rumen microflora structure. Therefore, it is believed that rumen microflora structure is the main mechanism regulating A: P ratio in rumen fermentation.