Determination of Lovastatin (mevinolin) and mevinolinic acid in fermentation liquids

A rapid and simple HPLC method for the determination of Lovastatin (mevinolin) and mevinolinic acid in fermentation fluids of Aspergillus terreus using a Separon SGX C₁₈ column and methanol-18 mM orthophosphoric acid (77.5:22.5, v/v) as mobile phase with detection at 238 nm is described. The detection limit of Lovastatin and mevinolinic acid was 20–30 ng/ml.     

Synthesis and kinetic study of hydrolysis of di‐2‐chloroaniline phosphate ester in acidic medium

The kinetics and mechanism of the acid‐catalyzed hydrolysis of di‐2‐chloroaniline phosphate ester were studied in 0.5–7.0 mol dm^?3 hydrochloric acid at 80°C in 20/80 (v/v) dioxane–water medium. The log rate profile shows rate maximum at 4.0 mol dm^?3 hydrochloric acid. The results show that di‐2‐chloroaniline phosphate is reactive mainly via conjugate acid species. Ionic strength data show a positive salt effect. The effect of different parameters such as temperature, solvent, and substrate concentration on the rate of hydrolysis was studied. Molecularity and order of the reaction have been supported by Arrhenius parameters, the Zucker–Hammett hypothesis. The rate values shown by experimental and theoretical computational hold good agreements in the entire acid range. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 42: 126–131, 2010     

Ester hydrolysis and enol nitrosation reactions of ethyl cyclohexanone-2-carboxylate inhibited by beta-cyclodextrin

Both the ester hydrolysis and the nitrosation reactions of the enol tautomer of ethyl cyclohexanone-2-carboxylate (ECHC) are investigated in the absence and presence of beta-cyclodextrin (beta-CD). The ester hydrolysis reaction is studied in dilute H2O and D2O solutions of hydrochloric acid and in aqueous buffered solutions of carboxylic acids (acetic acid and its chloro derivatives). The pseudo-first-order rate constant increases with both the [H+] and the total buffer concentration, indicating that the hydrolysis is subject to acid and general base catalysis. Substantial solvent isotope effects in the normal direction (kH/kD > 1) for the acid-catalyzed hydrolysis was observed. Addition of beta-CD strongly slows the hydrolysis reaction. The variation of the observed rate constant (k(o)) with [beta-CD] exhibits saturation behavior, consistent with 1:1 binding between the enol of ECHC and beta-CD. The binding is quite strong, and bound ECHC-enol is unreactive. The nitrosation reaction of ECHC in aqueous acid medium, using sodium nitrite in great excess over the concentration of ECHC, yields perfect first-order kinetics, indicating that the slow step is the nitrosation of the enol tautomer. This finding suggests that a great percentage of the total ECHC concentration must exist in the enol form. The nitrosation reaction is of first order in [nitrite] and is catalyzed by the presence of Cl-, Br-, or SCN- ions, which indicates that the attack of the nitrosating agent is the slow step. The nitrosation reaction is also strongly inhibited by the presence of beta-CD because of the formation of unreactive inclusion complexes between the host, beta-CD, and the guest, the enol of ECHC. In alkaline medium, the formation of the enolate ion is observed, which absorbs at higher wavelengths (lambda(max) = 256 nm in acid medium shifts to lambda(max) = 288 nm in alkaline medium). This anion also undergoes ester hydrolysis spontaneously, but shows neither specific basic catalysis nor appreciable effect by the presence of beta-CD. From kinetic and spectroscopic measurements the pKa of the enol of ECHC has been determined as 12.35.     

Intramolecular migration of long chain acyl group of enacyloxin IIa methyl ester

Enacyloxin IIa methyl ester in non-protic solvent gave rearranged product in acidic conditions such as surface of TLC plate of silica gel or by treatment with a catalytic amount of p-toluenesulfonic acid. On the other hand, such a rearrangement did not occur in polar protic solvent. The structure of the rearranged product was elucidated as 4-acyl analog of the cyclohexane ring.     

Solvent Effects in Acid‐Catalyzed Biomass Conversion Reactions

Reaction kinetics were studied to quantify the effects of polar aprotic organic solvents on the acid‐catalyzed conversion of xylose into furfural. A solvent of particular importance is γ‐valerolactone (GVL), which leads to significant increases in reaction rates compared to water in addition to increased product selectivity. GVL has similar effects on the kinetics for the dehydration of 1,2‐propanediol to propanal and for the hydrolysis of cellobiose to glucose. Based on results obtained for homogeneous Brønsted acid catalysts that span a range of pK_a values, we suggest that an aprotic organic solvent affects the reaction kinetics by changing the stabilization of the acidic proton relative to the protonated transition state. This same behavior is displayed by strong solid Brønsted acid catalysts, such as H‐mordenite and H‐beta.     

酸性药物的反向电渗流高效毛细管电泳分离分析研究

以水杨酸、乙酰水杨酸为代表药物,采用十六烷基三甲基溴化铵（ＣＴＡＢ）为电渗流改向剂,考察了酸性药物在反向电渗流高效毛细管电泳体系中的分离行为,并对其中影响迁移时间、峰形及柱效的诸多因素进行了系统研究。研究结果表明,以阳离子表面活性剂作为电渗流改向剂的反向电渗流高效毛细管电泳体系能显著加快酸性药物的分析速度。对于ＣＴＡＢ与酸性药物相互作用导致峰形展宽、柱效降低的现象,可通过加入合适的有机添加剂（如β－环糊精或乙腈）加以改善。     

Solvent and concentration effects on the visible spectra of tri-para-dialkylamino-substituted triarylmethane dyes in liquid solutions

We have characterized the spectroscopy properties of crystal violet (CV+) and ethyl violet (EV+) in liquid solutions as a function of the solvent type and dye concentration. The analysis of how solvent properties and dye concentration affects the electronic spectra of these tri-para-dialkylamino substituted tryarylmethane (TAM+) dyes was performed on the basis of two spectroscopic parameters, namely the difference in wavenumber (deltanu) between the maximum and the shoulder that appears in the short-wavelength side of the respective maximum visible band (deltanu = 1/lambda(shoulder)-1/lambda(max) cm(-1)), and the wavelength of the maximum absorption (lambda(max)). The solvent and the concentration effects on lambda(max) and deltanu have indicated that both solute/solute (ion-pairing and dye aggregation) and solute/solvent (H-bonding type) interactions modulate the shape of the visible electronic spectra of these dyes in solution. In solvent with small dieletric constant (epsilon < approximately 10), the formation of ion-pairs represents a major contribution to the shaping of these spectra. Upon increasing dye concentration the formation of ion-pairs was characterized by an increase in deltanu observed concomitantly with a red shift in lambda(max) In chloroform and chlorobenzene the ion-pair association constant of CV+ and EV+ with Cl- ions were found to be in the order of 10(6) and 10(5) M(-1), respectively. In trichloroethylene the association constant for the CV+Cl- pair was 10(8) M(-1). In water, dye aggregation instead of ion-pairing represents a major contribution to the shaping of the visible spectra of CV+ and EV+. Dye aggregation was indicated by an increase in deltanu observed concomitantly with a blue shift in lambda(max) upon increasing dye concentration. The distinct behavior of deltanu for dye aggregation and ion-pairing as a function of dye concentration can therefore assist in the characterization of these two distinct phenomena. The solute/solvent interactions were studied in a series of polar solvents in which solute/solute interactions do not occur in any detectable extent. The dependence found for deltanu as a function of the Kamlet-Tafts solvatochromic parameters (alpha, beta and pi*) is in keeping with previous inferences indicating that the splitting in the overlapped absorption band of CV+ and EV+ in hydroxilated solvents arises from a perturbation in the molecular symmetry induced by hydrogen bonding (donor-acceptor) type interactions with solvent molecules. A distinction between the effects of solute/solute and solute/solvent interactions on the visible spectra of these dyes is provided.     

Enantiopure Aminopyrans by a Lewis Acid Promoted Rearrangement of 1,2‐Oxazines: Versatile Building Blocks for Oligosaccharide and Sugar Amino Acid Mimetics

1,3‐Dioxolanyl‐substituted 1,2‐oxazines, such as syn‐ 1 and anti‐ 1 , rearrange under Lewis acidic conditions to provide bicyclic products 2 – 5 . Subsequent reductive transformations afforded enantiopure 3‐aminopyran derivatives such as 7 and 9 or their protected diastereomers 16 and 18 , which can be regarded as carbohydrate mimetics. An alternative sequence of transformations including selective oxidation of the primary hydroxyl groups in 21 and 24 led to two protected β‐amino acid derivatives with carbohydrate‐like backbone (sugar amino acids). Treatment of bicyclic ester 23 with samarium diiodide cleaved the N? O bond and furnished the unusual β‐lactam 27 in excellent yield. Alternatively, γ‐amino acid derivative 29 was efficiently prepared in a few steps. Fairly simple transformations gave azides 32 and 35 or alkyne 30 which are suitable substrates for the construction of oligosaccharide mimetics such as 34 by copper iodide catalyzed cycloadditions. With this report we demonstrate that enantiopure rearrangement products 2 – 5 are protected precursors of a variety of polyfunctionalized pyran derivatives with great potential for chemical biology.     

酸性药物在微乳液相色谱体系中的保留行为

以酸性药物萘普生、布洛芬、双氯芬酸、苯丙氨酸和2,4-二氯苯氧基乙酸为研究对象,探讨了酸性药物在微乳液相色谱体系中保留机理,建立了酸性药物的容量因子(k′)与表面活性剂浓度、助表面活性剂浓度、亲脂性有机溶剂浓度以及流动相pH值之间的相关模型。结果表明,表面活性剂、助表面活性剂和亲脂性有机溶剂的浓度以及流动相pH值的变化对酸性药物的容量因子的影响完全与理论模型相吻合。所建立的保留模型能较好地反映在微乳液相色谱体系中微乳液组成和pH值对酸性药物保留行为的影响。     

Impact of solvent conditions on separation and detection of basic drugs by micro liquid chromatography-mass spectrometry under overloading conditions

In this study the impact of solvent conditions on the performance of μLC/MS for the analysis of basic drugs was investigated. Our aim was to find experimental conditions that enable high-performance chromatographic separation particularly at overloading conditions paired with a minimal loss of mass spectrometric detection sensitivity. A focus was put on the evaluation of the usability of different kinds of acidic modifiers (acetic acid (HOAc), formic acid (FA), methansulfonic acid (CH₃SO₃H), trifluoroacetic acid (TFA), pentafluoropropionic acid (PFPA), and heptafluorobutyric acid (HFBA)). The test mixture consisted of eleven compounds (bunitrolol, caffeine, cocaine, codeine, diazepam, doxepin, haloperidol, 3,4-methylendioxyamphetamine, morphine, nicotine, and zolpidem). Best chromatographic performance was obtained with the perfluorinated acids. Particularly, 0.010–0.050% HFBA (v/v) was found to represent a good compromise in terms of chromatographic performance and mass spectrometric detection sensitivity. Compared to HOAc, on average a 50% reduction of the peak widths was observed. The use of HFBA was particularly advantageous for polar compounds such as nicotine; only with such a hydrophobic ion-pairing reagent chromatographic retention of nicotine was observed. Best mass spectrometric performance was obtained with HOAc and FA. Loss of detection sensitivity induced by HFBA, however, was moderate and ranged from 0 to 40%, which clearly demonstrates that improved chromatographic performance is able to compensate to a large extent the negative effect of reduced ionization efficiency on detection sensitivity. Applications of μLC/MS for the qualitative and quantitative analysis of clinical and forensic toxicological samples are presented.     

Coloured complexes of all-trans-retinal with benzocaine and other local anaesthetics

Coloured Schiff base complexes with lambda max values of 500 nm or above were formed between the visual pigment all-trans-retinal and the local anesthetics procaine (lambda max = 533 nm), benzocaine (4-amino-benzoic acid ethyl ester, lambda max = 535 nm), 3-amino-benzoic acid ethyl ester (lambda max = 500 nm) and 2-amino-benzoic acid ethyl ester (lambda max = 509 nm) in methanol acidified with HCl. The anaesthetics lidocaine and urethane failed to form coloured compounds with lambda max values greater than 500 nm under the same conditions. The relevance of these observations to the effect of anaesthetics on the visual pigments is discussed.     

Characteristics of acrylic acid-grafted polyethylene prepared by photografting using mixed solvents consisting of water and organic solvent

Photografting of acrylic acid (AA) on linear-low density polyethylene film (thickness=30 μm) was investigated at 60 °C using mixed solvent consisting of water and organic solvents such as acetone and methanol. Xanthone was used as photoinitiator, which was coated on the film earlier. With longer photoirradiation time, such as 40 and 60 min, the percentage of grafting decreased with increasing the concentration of organic solvent in the mixed solvent, where formation of homopolymer occurred preferentially over the grafting reaction. In the system with photoirradiation of 20 min, on the other hand, a maximum percentage of grafting was observed at a certain concentration of organic solvent, in which formation of grafted polymer rather than homopolymer was emphasized. Photografting using the mixed solvent resulted in AA-grafted film with homogeneous distribution of grafted chains, exhibiting larger pH-responsive character, where the grafted film shrinks in an acidic medium, while it swells in an alkaline region. Polymer catalysts for hydrolysis of p-nitrophenylacetate, which was performed at 40 °C in water/ethanol (1/4, v/v)-mixed solvent at pH=9.0, could be prepared by reacting the AA-grafted film with L-histidine and its catalytic activity was slightly influenced by location of grafted chains.     

KCD/MDEA/TA三元引发剂引发丙烯酸酯/液晶复合体系光聚合动力学

采用配有441.6 nm滤光片的光差示扫描量热仪研究了3,3'-羰基双(7-二乙胺香豆素)(KCD)/N-甲基二乙醇胺(MDEA)/2-(4-甲氧苯基)-4,6-双(三氯甲基)-1,3,5-三嗪(TA)三元引发剂引发丙烯酸酯/液晶复合体系光聚合动力学行为. 结果表明, 在KCD/MDEA复合引发剂中添加TA, 显著提高了丙烯酸酯/液晶复合体系的最大光聚合速率[R_p(max)]和单体转化率, 当TA质量分数为0.5%时, 体系的R_p(max)和单体转化率分别提高了100%和69%. 同时, 随着光照强度的增加, 该体系的R_p(max)和单体转化率呈增大的趋势, 当光强从1.5 mW/cm⁺²提高到35.2 mW/cm⁺²时, 其R_p(max)和最终单体转化率分别提高了2.5和2.8倍.     

Enantioresolution of basic pharmaceuticals using cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral stationary phase and polar organic mobile phases

A polysaccharide-based chiral stationary phase (Sepapak-4), with cellulose tris(4-chloro-3-methylphenylcarbamate) as chiral selector, has been investigated in liquid chromatography (LC). Its enantioresolution power was evaluated towards 13 basic amino-drugs with widely different structures and polarities, using polar organic mobile phases. After preliminary experiments, acetonitrile was selected as the main mobile phase component, to which a low concentration of diethylamine (0.1%) was systematically added in order to obtain efficient and symmetrical peaks. Different organic solvents were first added in small proportions (5–10%) to acetonitrile to modulate analyte retention. Polar organic modifiers were found to decrease retention and enantioresolution while hexane had the opposite effect, indicating normal-phase behaviour under these conditions. The addition of an organic acid (formic, acetic or trifluoroacetic acid) was found to strongly influence the retention of the basic amino drugs in these nonaqueous systems. The nature and proportion of the acidic additive in the mobile phase had also deep impact on enantioresolution. Therefore, the studied compounds could be subdivided in three groups in respect to the acidic additive used. All analytes could be enantioseparated in relatively short analysis times (10–20 min) using these LC conditions.     

HYDROLYSIS OF N-(METHOXYCARBONYL-OR ISOPROPYLCARBAMOYL-METHOXYPHOSPHONYL)-α-AMINO ACID ESTERS

Abstract

The hydrolysis of the title compounds was studied in order to investigate the possibility of their usage as drugs or pesticides. It was found that there were two different pathways of hydrolysis according to the pH region of the solution. In the acidic pH region, the P-N bond cleaves for the both compounds. In the basic pH region, the P-C and P-O bonds would cleave for the compound of N-(methoxycarbonyl-methoxyphosphonyl)-α-amino acid ester (I). While for the compound of N-(isopropylcarbamoyl-methoxyphosphony1)-α-amino acid ester (11). only the P-O bond cleaves. The possible mechanism is discussed.     

Synthetic studies related to compactin and mevinolin: A new synthesis of the lactone system.

(S)-Malic acid diethyl ester was converted into a precursor of the lactonic portion of compactin and mevinolin. The substance was coupled with benzyl $\text{p}$-tolyl sulfone and elaborated into the chiral lactone system of the natural products.     

HPLC Post-Column Ion-Pair Extraction of Acidic Drugs Using a Substituted α-Phenylcinnamonitrile Quaternary Ammonium Salt as a New Fluorescent Ion-Pair Reagent

Abstract

A reversed-phase HPLC post-column ion-pair extraction system was developed for the analysis of carboxylic acid drugs and their salts using α-(3,4-dimethoxyphenyl)-4′ -trimethylammonium-methylcinnamonitrile methosulfate (DTM) as a new fluorescent ion-pair reagent. The on-line post-column extraction system was optimized with respect to the reagent concentration, extraction coil length and internal diameter, ionic strength of mobile phase, extraction solvent, and the membrane phase separator. Sodium salicylate, ketoprofen, ibuprofen, probenecid, and valproic acid were used as model compounds to evaluate the ion-pair extraction system. The method was applied to pharmaceutical dosage forms containing ketoprofen and valproic acid. Other acidic compounds evaluated using the ion-pair reagent showed that lipophilic acids produced more extractable ion-pairs and higher sensitivities than hydrophilic acids.     

Hydrotrope-induced autocatalysis in the biphasic alkaline hydrolysis of aromatic esters

The alkaline hydrolysis of aromatic esters exhibits autocatalytic kinetics when performed under two-phase conditions without any mixing solvent. The molecular structures of such aromatic esters determine whether the autocatalysis occurs or not. It has been established that enhancing the solubility of the hydrophobic ester in water by the hydrotropic salts yielded by the hydrolysis itself accelerates the apparent reaction rate. By kinetically independent measurements, the solubilization process of the ester was verified to be the rate-determining step. It has been observed that the solubilization process can be influenced by factors such as the initial addition of hydrotropic salt, the volumetric ratio of the oil/aqueous phase, and the concentration of alkali.     

Unusual phenomena during the resolution of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ): thermodynamic-kinetic control

6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) was resolved in several different solvents by tartaric acid derivatives as the most common acidic resolving agents available in industrial quantities. Strong reaction kinetics and solvent dependence were observed, curiously without solvation. In possession of these findings, an economic resolution process is proposed, which is completed by the incorporation of a racemization step.     

Cyclopentyl decanoate and butyl cyclopentanecarboxylate conversions into ketones over solid catalyst

Summary Cyclopentyl n-decanoate and n-butyl cyclopentanecarboxylate were converted into ketones over heterogeneous catalyst. The transformations proceeded as parallel ones: through b-ketoesters with simultaneous thermal decomposition (retro-Tishchenko reaction) and secondary condensation of the resultant aldehydes. The path from esters to ketones from acidic ester sides is shorter than the one from alcohol ester sides. The mutual proportions of ketones depend also on the control parameters.