Total Synthesis of (−)‐Zampanolide and Structure–Activity Relationship Studies on (−)‐Dactylolide Derivatives

A new total synthesis of the marine macrolide (?)‐zampanolide ( 1 ) and the structurally and stereochemically related non‐natural levorotatory enantiomer of (+)‐dactylolide ( 2 ), that is, ent‐ 2 , has been developed. The synthesis features a high‐yielding, selective intramolecular Horner–Wadsworth–Emmons (HWE) reaction to close the 20‐membered macrolactone ring of 1 and ent‐ 2 . The β‐keto phosphonate/aldehyde precursor for the ring‐closure reaction was obtained by esterification of a ω‐diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent‐ 2 . THP ring formation was accomplished through a segment coupling Prins‐type cyclization. Employing the same overall strategy, 13‐desmethylene‐ent‐ 2 as well as the monocyclic desTHP derivatives of 1 and ent‐ 2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro with nM IC₅₀ values, while ent‐ 2 , which lacks the diene‐containing hemiaminal‐linked side chain of 1 , is 25‐ to 260‐fold less active. 13‐Desmethylene‐ent‐ 2 as well as the reduced versions of ent‐ 2 and 13‐desmethylene‐ent‐ 2 all showed similar cellular activity as ent‐ 2 itself. The same activity level was attained by the monocyclic desTHP derivative of 1 . Oxidation of the aldehyde functionality of ent‐ 2 gave a carboxylic acid that was converted into the corresponding N‐hexyl amide. The latter showed only μM antiproliferative activity, thus being several hundred‐fold less potent than 1 .     

Synthesis of a Novel C2‐Symmetric Bis‐oxazoline (=Bis[4,5‐dihydrooxazole]) and Its Application as Chiral Ligand in Asymmetric Transition Metal Catalysis

The new C₂‐symmetric bis‐oxazoline (=bis[4,5‐dihydrooxazole]) 2 with a chiral trans‐(2R,3R)‐2,3‐bis(3,5‐diphenylphenyl)cyclopropylidene (=trans‐(2R,3R)‐2,3‐bis([1,1′: 3′,1″‐terphenyl]‐5′‐yl)cyclopropylidene) backbone was efficiently synthesized (Scheme). All synthetic steps were easy to perform and led to the desired product in good overall yields. Compound 2 was tested and compared as ligand in several enantioselective catalytic reactions such as palladium(0)‐catalyzed enantioselective allylic alkylations and copper(I)‐catalyzed enantioselective cyclopropanations and aziridinations.     

Analysis of colistin sulfate by capillary zone electrophoresis with cyclodextrins as additive

A method for the quantitative analysis of colistin sulfate by capillary zone electrophoresis is described. Since colistin components have five free amino groups, they tend to adsorb onto the capillary wall and cause peak tailing. It was found that triethanolamine (TEA)-phosphate buffer at pH 2.5 was useful to reduce such adsorption. Methyl-beta-cyclodextrin (M-beta-CD) and 2-propanol (IPA) were found necessary for selectivity enhancement. In order to optimize the separation parameters and predict the method robustness, a central composite design was performed including three variables, namely concentration of M-beta-CD, TEA, and IPA. The effects of capillary length and applied voltage on separation were also investigated. The optimal conditions established were: 140 mM TEA-phosphate buffer containing 5 mM M-beta-CD and 6% v/v IPA, a capillary with 55 cm total length (50 microm inner diameter, 47 cm from inlet to detection window) and 24 kV applied voltage. The method was found to be robust when the variables were changed in the following range: 4-6 mM M-beta-CD, 5-7% v/v IPA, and 130-150 mM TEA. Further, the linearity, limit of detection (LOD), and limit of quantitation (LOQ), as well as repeatability for both colistin A and B were examined and three commercial samples were quantitatively analyzed.     

Capillary electrophoresis analysis of gentamicin sulphate with UV detection after pre-capillary derivatization with 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid

A selective, sensitive, and rapid pre-capillary derivatization method for determination of the multicomponent aminoglycoside antibiotic gentamicin is described. The derivatization reagents 1,2-phthalic dicarboxaldehyde and mercaptoacetic acid were used and the thioisoindole derivative was UV detected at 330 nm. A central composite experimental design was performed to optimize selectivity and derivatization conditions. Baseline separation of gentamicin C1, C1a, C2, C2a, C2b, sisomicin and several minor components was achieved with a background electrolyte containing 30 mM sodium tetraborate, 7.5 mM beta-cyclodextrin and 12.5% (v/v) methanol at pH 10. Quantitative analysis was performed and illustrated the potential use of capillary electrophoresis for the identification and quantitation of gentamicin as an alternative to methods prescribed in the United States Pharmacopeia and European Pharmacopoeia.     

Scope and limitations of a new highly selective synthesis of unsymmetrical monomers for the synthesis of precursors toward poly(arylenevinylene)s

In our laboratory a precursor route to poly(p-phenylenevinylene) derivatives is developed in which unsymmetrically substituted p-xylene derivatives, possessing a benzylic sulfinylalkyl group, are used as monomers. Because of this unsymmetry, we were forced to investigate thoroughly the synthesis of these sulfoxides, as we start from symmetric and readily accessible molecules, namely, bis(halomethyl)-p-xylene derivatives. In a former publication, a new extremely effective route for the production of these unsymmetrically substituted sulfinyl monomers was presented. This paper expands upon these previously reported results. To examine the scope and limitations of this elegant route, this new method was applied to the synthesis of various derivatives not included in the initial work.     

Influence of temperature and UV intensity on photo-polymerization reaction studied by photo-DSC

Photo-DSC was used to investigate the cure kinetics of a photo-initiated resin. The exothermal photo-polymerization reactions were performed in isothermal mode. The irradiation of photo-initiated resin was studied under different conditions of temperature, UV lamp intensity, and reaction atmosphere (nitrogen and air). The results obtained by photo-DSC allowed us to determine kinetic data of the photo-polymerized reactions: the global activation energy and reaction enthalpy, and the conversion as a function of time and temperature. Modulated temperature DSC measurements were carried out to verify whether vitrification occurs during polymerization. The conversion at the top and bottom of irradiated samples was obtained by FT-IR spectroscopy before and after photo-polymerization. A non-homogenous photo-polymerization into the material was observed, probably because of the light absorptions effects within the uppermost layers.     

Adsorption of hydrocarbons from solutions and gas phase on silica and alumina modified with silver and gold ions

The paper reports the immobilization of Ag⁺ cations on alumina and silica and AuCl ₄ ^? anions on amino silica and alumina. The method of inverse gas chromatography have demonstrated that Ag(I)-silica is selective for the separation of alkanes, alkenes, alkines, and arenes. The dependence of the capacitance of Ag(I) and Au(III) composites with regard to phenylacetylene (PHA) on the nature of the carriers, surface concentration, and technique of immobilizing ion metals has been considered. The isotherms of the adsorption of PHA from solutions in octane have been measured. It has been revealed that the capacitance of composites with regard to toward PHA prepared by the immobilization of ammoniates of silver nitrate on silicon dioxide is several times higher than for composites based on alumina with the same silver concentration and composites prepared by the immobilization of silver nitrate on silicon dioxide. The capacitance of the Au(III) composite based on alumina for PHA is significantly higher than for that based on aluminum oxide. The highest capacitance for PHA (0.83 and 0.88 molecules per metal ion) is observed for Ag(I) silica and the Au(III) alumina composite. In the visible region, the diffuse reflection spectra of amino silica Au(III) composites have a significant shift of the maximum of adsorption band along with the decrease in the concentration of immobilized anions of AuCl ₄ ^? , which evinces the formation of coordination bonds between free amin?propyl groups of the silica carrier and gold atom. The formation of these bonds prevents the adsorption of PHA on amino silica Au(III) composites with low gold concentrations.     

Naphthalene Complexation by β-Cyclodextrin: Influence of Added Short Chain Branched and Linear Alcohols

Naphthalene forms 1 : 1 complexes with -cyclodextrin (-CD)in water. The binding constant is 377 ± 35 M^-1. Addition of linear or branched alcohols causes a reduction in the apparent strength of naphthalene binding (K_app) compared to the value in the absence of additives. For example, 1% 1-pentanol reduces K_app to 184 ± 31 M^-1. Branching does not alter K_app much for a given number of carbon atoms, e.g., it is 113 ± 9 M^-1for 2-pentanol and 116 ± 8 M^-1for 3-pentanol. The exception to this is tert-butanol for which K_app is 577 ± 40 M^-1. The variation in K_app as a function of [1-pentanol] yields values for the individual equilibrium constants contributing to K_app. This reveals that a ternary complex forms involving naphthalene, the CD and 1-pentanol. The constant for formation of the ternary complex is 99 ± 29 M^-2. NaI quenching of naphthalene fluorescence indicates that the CD cavity partially protects the naphthalene excited state fromthis water phase quencher. Interestingly, the Stern–Volmer constant is lower in the presence of 1-pentanol than in its absence, although there should be more unbound (and therefore more NaI accessible) naphthalene in the former system than in the latter. These apparently contradictory results are discussed in terms of ternary complex formation.     

Validation studies and proficiency testing

Genetically modified organisms (GMOs) entered the European food market in 1996. Current legislation demands the labeling of food products if they contain <1% GMO, as assessed for each ingredient of the product. To create confidence in the testing methods and to complement enforcement requirements, there is an urgent need for internationally validated methods, which could serve as reference methods. To date, several methods have been submitted to validation trials at an international level; approaches now exist that can be used in different circumstances and for different food matrixes. Moreover, the requirement for the formal validation of methods is clearly accepted; several national and international bodies are active in organizing studies. Further validation studies, especially on the quantitative polymerase chain reaction methods, need to be performed to cover the rising demand for new extraction methods and other background matrixes, as well as for novel GMO constructs.     

A facile approach to architecturally defined nanoparticles via intramolecular chain collapse

A novel approach is presented for the controlled intramolecular collapse of linear polymer chains to give well-defined single-molecule nanoparticles whose structure is directly related to the original linear polymer. By employing a combination of living free radical polymerization and benzocyclobutene (BCB) chemistry, nanoparticles can be routinely prepared in multigram quantities with the size being accurately controlled by either the initial degree of polymerization of the linear chain or the level of incorporation of the BCB coupling groups. The latter also allows the cross-link density of the final nanoparticles to be manipulated. In analogy with dendritic macromolecules, a significant reduction of up to 75% in the hydrodynamic volume is observed on going from the starting random coil linear chains to the corresponding nanoparticles. The facile nature of the living free radical process also permits wide variation in monomer selection and functional group incorporation and allows novel macromolecular architectures to be prepared. Furthermore, the use of block copolymers functionalized with benzocyclobutene groups in only one of the blocks gives, after intramolecular collapse, a hybrid architecture in which a single linear polymer chain is attached to the globular nanoparticle.