A direct stereoselective approach to trans-2,3-disubstituted piperidines: application in the synthesis of 2-Epi-CP-99,994 and (+)-epilupinine

A simple synthesis of enantiomerically pure piperidine esters is described, offering a straightforward access to the trans-2,3-disubstituted piperidine skeleton which is present in a broad range of biologically active compounds.     

L-selectride-mediated highly diastereoselective asymmetric reductive aldol reaction: access to an important subunit for bioactive molecules

L-selectride reduction of a chiral or achiral enone followed by reaction of the resulting enolate with optically active alpha-alkoxy aldehydes proceeded with excellent diastereoselectivity. The resulting alpha,alpha-dimethyl-beta-hydroxy ketones are inherent to a variety of biologically active natural products.     

Simple and rapid extraction, separation, and detection of alkaloids in beverages

Implementation of an uncomplicated SPE process for the rapid extraction and preconcentration of the alkaloids, colchicine, strychnine, aconitine, and nicotine, from water, apple juice, and nonfat milk samples is presented. When coupled to analysis via micellar EKC (MEKC), the total analysis time per sample was less than 15 min for the water and juice samples and less than 20 min for the milk. The SPE process allowed for anywhere from a three to a fourteen-fold improvement in the LOD for each alkaloid when compared to detecting the alkaloids in a nontreated water sample matrix. Following SPE, the LODs for colchicine, strychnine, and nicotine were sufficient to meet levels from 150 to 5000 times more dilute than the LD(50) for a 50 kg individual drinking 12 oz of a contaminated beverage. Aconitine, on the other hand, was detected at approximately the LD(50) level. The percent recoveries for the SPE ranged from 37% to as high as 99%. Nicotine attained the highest recovery efficiencies, followed by colchicine, and finally, aconitine and strychnine, which were nearly identical. The greatest recovery efficiencies were achieved from apple juice and water, whereas nonfat milk yielded the lowest.     

Fast, noninvasive and simultaneous near-infrared spectroscopic characterisation of physicochemical stationary phases' properties: from silica particles towards monoliths

The design of novel stationary phases is a permanent demanding challenge in chromatographic separation science to enable analysis with enhanced selectivity, specificity and speed. Therefore, the characterisation of chemical and physical properties is next to calculation of chromatographic parameters essential. Conventionally, chemical parameters including surface coverage are determined by burning combustion or frontal analysis, physical parameters including particle size, pore size, pore volume and surface area are determined by SEM, mercury intrusion porosimetry (MIP) and Brunauer-Emmett-Teller (BET). All these methods are time consuming, invasive and require besides special equipment some special trained laboratory staff. Therefore, we introduced near-infrared spectroscopy (NIRS) as a noninvasive, easy-to-handle technology with wavenumber ranging from 4000 to 10,000 cm(-1) enabling analysis within only a few seconds at higher precision than the conventional methods. Investigated materials comprise porous and nonporous silica gel, carbon-based nanomaterials (fullerenes), polymer beads and monoliths. Different carriers themselves and their kind of derivatisations (RP, normal-phase, ion-exchanger, IMAC (immobilised metal affinity chromatography), affinity) can be determined by applying principal component analysis (PCA) of recorded spectra. Partial least square regression (PLSR) enables the determination of particle size, pore size, pore volume, porosity, total porosity and surface area with one single measurement. For the optimised design of well-defined polymer beads and monoliths, real-time in situ monitoring to control, e. g. particle and pore sizes as well as monomer content during the polymerisation process, can be extremely helpful. In this article, the advantages of this fast, noninvasive high-throughput NIRS methods are summarised, discussed in detail and different applications of the individual characterised materials are shown.     

Synthesis of Aryl- and Alkyl-Containing 3-Methylene-5-hydroxy Esters via a Barbier Allylation Reaction

The formation of C−C bonds via the allylation of carbonyl compounds has been widely applied in total syntheses. Amongst the many possible strategies, the Barbier-type allylation in aqueous media has received only moderate attention over the last decades despite its mild reaction conditions. In this study, we investigated the indium (In⁰) and zinc (Zn⁰) mediated Barbier allylation reaction to efficiently synthesize base-labile 3-methylene-5-hydroxy containing building blocks for natural product total synthesis. As model study we selected the allylation of lipidic undecanal with ethyl 3-(bromomethyl)but-3-enoate in the presence of either Zn⁰ or In⁰ and investigated the effects of additives on yields and selectivities. We then applied the optimized reaction conditions to sterically demanding allyl bromides and functionalized aromatic aldehydes yielding eleven new homoallylic alcohols, one of which was further transformed via oxidation and reduction sequences.     

Vibrational Predissociation Spectra of C2N− and C3N−: Bending and Stretching Vibrations

We present infrared predissociation spectra of C₂N⁻(H₂) and C ₃N⁻(H₂) in the 300–1850 cm⁻¹ range. Measurements were performed using the FELion cryogenic ion trap end user station at the Free Electron Lasers for Infrared eXperiments (FELIX) laboratory. For C₂N⁻(H₂), we detected the CCN bending and CC−N stretching vibrations. For the C₃N⁻(H₂) system, we detected the CCN bending, the CC−CN stretching, and multiple overtones and/or combination bands. The assignment and interpretation of the presented experimental spectra is validated by calculations of anharmonic spectra within the vibrational configuration interaction (VCI) approach, based on potential energy surfaces calculated at explicitly correlated coupled cluster theory (CCSD(T)-F12/cc-pVTZ−F12). The H₂ tag acts as an innocent spectator, not significantly affecting the C_2,3N⁻ bending and stretching mode positions. The recorded infrared predissociation spectra can thus be used as a proxy for the vibrational spectra of the bare anions.     

Structure-activity relationships for the fluorescence of ochratoxin A: insight for detection of ochratoxin A metabolites

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium that is widely found as a contaminant of food products. The toxin is a renal carcinogen in male rats, the cause of mycotoxicoses in pigs and has been associated with chronic human kidney diseases. Bioactivation has been implicated in OTA-mediated toxicity, although inconsistent results have been reported, due, in part, to the difficulty in detecting OTA metabolites in vivo. Liquid chromatography (LC) coupled with fluorescence detection (FLD) is the most widely used analytical detection method for OTA. Under acidic conditions the toxin generates blue fluorescence (465 nm) that is due to an excited state intramolecular proton transfer (ESIPT) process that generates an emissive keto tautomer. Disruption of this ESIPT process quenches fluorescence intensity and causes a blue shift in emission maxima. The aim of the present study was to determine the impact of the C5-chlorine atom, the lactone moiety and the amide bond on OTA fluorescence and derive optical parameters for OTA metabolites that have been detected in vitro. Our results highlight the limitations of LC/FLD for OTA metabolites that do not undergo ESIPT. For emissive derivatives, our absorption and emission data improves the sensitivity of LC/FLD (3-4-fold increase in the limit of detection (LOD)) for OTA analogues bearing a C5-OH group, such as the hydroquinone (OTHQ) metabolite and the glutathione conjugate of OTA (OTA-GSH). This increased sensitivity may facilitate the detection of OTA metabolites bearing a C5-OH group in biological fluids and enhance our understanding of OTA-mediated toxicity.     

High-Performance Liquid Chromatographic Determination of Cefepime and Cefazolin in Human Plasma and Dialysate

A simple high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of cefepime and cefazolin in human plasma and dialysate. For component separation, the method utilized a C₁₈ column with an aqueous mobile phase of dibasic potassium hydrogen phosphate (pH 7.0) and methanol gradient at a flow rate of 1 mL min⁻¹. The method demonstrated linearity from 2.0 to 100.0 μg mL⁻¹ (r > 0.999) with detection limit of 1 μg mL⁻¹ for both cefepime and cefazolin. The method was utilized for evaluation of plasma and dialysate samples in a clinical study evaluating the dialyzer clearance of cefepime and cefazolin using high-flux hemodialysis with varying blood flow rates in chronic kidney failure patients undergoing hemodialysis and peritoneal dialysis treatment.     

Capillary liquid chromatography-mass spectrometry for the rapid identification and quantification of almond flavonoids

A rapid negative ion ESI high-performance capillary liquid chromatography-mass spectrometry method was developed to identify and quantify flavonoids (e.g., flavanols, flavonols, flavanones and glycosides). Fifteen standards and two varieties of almond skin extract powder (Carmel and Nonpareil) were used to demonstrate the chromatographic separation, reproducibility and accuracy of the method that employed a 150 mm x 0.3 mm ChromXP 3C18-EP-120 column. All standards eluted in less than 10 min, providing a 9-12x reduction in analysis time compared to existing methods (90-120 min). However, isomers (e.g., catechin/epicatechin and galactosides/glucosides) were not resolved and, therefore, identified and quantified collectively. RSDs for retention time and peak area reproducibility (mass spectrometry data) were <0.5% and <5.0%, respectively. Peak area reproducibility was greatly improved (from a RSD>10%) after the implementation of a low-flow metal needle in the ESI source. Quantitation by mass spectrometry also afforded a % error less than 5% for most compounds.     

Unexpected formation of pyridodiindole derivatives with cytotoxic activity via double nenitzescu reaction

The title compounds 10 and 11 were prepared by a one‐step procedure from 1,4‐benzoquinone ( 4 ) and pyridine‐2,4,6‐triamine ( 5 ) via an extension of the Nenitzescu reaction