Total Syntheses of (−)‐Minovincine and (−)‐Aspidofractinine through a Sequence of Cascade Reactions

We report 8‐step syntheses of (?)‐minovincine and (?)‐aspidofractinine using easily available and inexpensive reagents and catalyst. A key element of the strategy was the utilization of a sequence of cascade reactions to rapidly construct the penta‐ and hexacyclic frameworks. These cascade transformations included organocatalytic Michael‐aldol condensation, a multistep anionic Michael‐S_N2 cascade reaction, and Mannich reaction interrupted Fischer indolization. To streamline the synthetic routes, we also investigated the deliberate use of steric effect to secure various chemo‐ and regioselective transformations.     

Complexation of hydroxamate-based siderophores with cobalt(II/III): growth inhibitory effect of cobalt(III)-desferricoprogen complex on fungi

Solution equilibrium results for Co(II) and Co(III) complexes of two natural hydroxamate-based siderophores, the exocyclic desferricrocin (DFR) and the endocyclic triacetylfusarinine (TAF) are presented. The three hydroxamate chelating functions of TAF were found to complete the octahedral coordination sphere of a Co(II) ion in stepwise processes, but following the coordination of two hydroxamates of DFR practically in one step, the third function, most probably because of sterical reasons, remained uncoordinated. A comparison with corresponding results for the previously studied acyclic desferrioxamine B (DFB) and desferricoprogen (DFC) provided some information about the effects of the molecular framework of siderophores on their cobalt-binding ability. The oxidation of the central metal ion under basic conditions and investigation of the cobalt(III) complexes by cyclic voltammetry were also made. Compared to Fe(III), by several orders of magnitude, higher stability complexes were formed with Co(III). The possibility of any effect of the Co(III)-siderophore complex on microbial Fe(III) uptake was tested by investigation of the antifungal effect of Co(III)-DFC in comparison with that of CoCl₂ on two fungi cultures, Penicillium brevicompactum and Aspergillus fumigatus.     

New facile tandem route to oxo- and thioxo[1,2,4]triazolo[1,5-a]pyridinium salts

2-Arylsulfanyl- and benzylsulfanylpyridinium N-arylimides (2), easily available from tetrazolo[1,5-b]pyridinium salts (1), participate in 1,3-dipolar cycloaddition with aryl isothiocyanates and aryl isocyanates to result in formation of fused thioxo- and oxo[1,2,4]triazolium salts (5 and 12), respectively. This transformation is interpreted as a regular 1,3-cycloaddition followed by spontaneous elimination of the aryl- or benzylsulfanyl group. Formation of these triazolium salts can be followed--under appropriate reaction conditions--by ring-opening reactions to afford some new triazolyldienes (6). Recognition of the intermediate participation of the thiolate anion along the pathway 1 --> 5 allowed elaboration of a simple procedure to 5 implying a tandem reaction sequence.     

Synthesis of a 2,2'-bipyridyl functionalized oligovinylene-phenylene using Heck and Horner-Wadsworth-Emmons reactions and X-ray crystal structure of E-(4-(4-bromostyryl)phenyl)(methyl)sulfane

The synthesis of a new 2,2'-bipyridyl functionalized oligovinylenephenylene (OVP-5) containing a methyl protected thiol using Heck coupling and the Horner-Wadsworth-Emmons reaction and is described. A key step involving a diisopropylcarbodiimide promoted dehydration of a stable β-hydroxyphosphonate intermediate was identified. The structure of precursor E-(4-(4-bromostyryl)phenyl)(methyl)sulfane was determined using X-ray crystallography.     

Structure Determination of an Unusual [2.2]paracyclophane Derivative by NMR Spectroscopy

Our ongoing study on cycloaddition reactions of dienes with different dienophiles afforded a great variety of derivatives with interesting molecular structures and electronic behavior. A new type of angularly annelated [2.2]paracyclophane (3) has been synthesize by the Diels–Alder reaction of 4-(2-propenyl[2.2]paracyclophane (1) and 1,4-benzoquinone (2) under high pressure conditions. The structure determination of this compound has been achieved by NMR measurements and semiempirical calculations.     

Study of the interaction of structurally similar bioactive compounds by thin-layer chromatography

The interaction between steroids and cholesterol is studied by reversed-phase thin-layer chromatography (TLC) using TLC plates impregnated by cholesterol and methanol-water mixtures as the eluents. The R(M) values obtained are in linear correlation with the methanol concentration of the eluent. The slope obtained from the linear regression analysis, which is characteristic of the strength of interaction, is determined. Stepwise regression and principal component analysis are carried out to find a relationship between the physicochemical parameters of steroid drugs and the strength of the interaction, which is followed by nonlinear mapping and cluster analysis to visualize the obtained results. The results show that steric and electronic parameters of the steroid drugs have a significant effect on the strength of the interaction between these structurally similar molecules.     

Fluorous click chemistry as a practical tagging method

Highly efficient fluorous tagging methodology was developed based on catalytic 1,3-dipolar cycloaddition as the key step.     

Uncommon Interactions of Aliphatic Dicarboxylic Acids with Cyclodextrins

A relatively high and unexpected increase of inclusion complex stabilities could be detected in some half dissociated dicarboxylic acids (HA⁻ ions) with intramolecular H-bonding. The intermolecular hydrogen bonds between the protruding functional groups of the guest and the hydroxy groups of the host are known to enhance the stability of the cyclodextrin (CD) inclusion complexes. The enhanced inclusion of HA⁻ species is promoted, not by the intermolecular but by the intramolecular H-bond indirectly, resulting in a compact shape of the guest with more favourable space filling.     

Interaction of carbon monoxide with Au(111) modified by ion bombardment: a surface spectroscopy study under elevated pressure

Gold based model systems exhibiting the structural versatility of nanoparticle ensembles and being accessible for surface spectroscopic investigations are expected to provide new information about the adsorption of carbon monoxide, a key process influencing the CO oxidation activity of this noble metal in nanoparticulate form. Accordingly, in the present work the interaction of CO is studied with an ion bombardment modified Au(111) surface by means of a combination of photoelectron spectroscopy (XPS and UPS), sum frequency generation vibrational spectroscopy (SFG), and scanning tunneling microscopy (STM). While no adsorption was found on intact Au(111), data collected on the ion bombarded surface at cryogenic temperatures indicated the presence of stable CO adsorbates below 190 K. A quantitative evaluation of the C 1s XPS spectra and the surface morphology explored by STM revealed that the step edge sites created by ion bombardment are responsible for CO adsorption. The identification of the CO binding sites was confirmed by density functional theory (DFT) calculations. Annealing experiments up to room temperature showed that at temperatures above 190 K unstable adsorbates are formed on the surface under dynamic exposure conditions that disappeared immediately when gaseous CO was removed from the system. Spectroscopic data as well as STM records revealed that prolonged CO exposure at higher pressures of up to 1 mbar around room temperature facilitates massive atomic movements on the roughened surface, leading to its strong reordering toward the structure of the intact Au(111) surface, accompanied by the loss of the CO binding capacity.     

Amorphization of a crystalline active pharmaceutical ingredient and thermoanalytical measurements on this glassy form

Amorphization is nowadays a method that is frequently applied in the pharmaceutical industry. The primary aim of this study is to achieve the amorphization of clopidogrel hydrogen sulphate as an active pharmaceutical ingredient (API) with various solvents and to choose the most suitable one. A secondary aim was to determine the glass-transition temperature (T _g) of this API and to classify it as a good or poor glass former. To investigate the amorphous form, differential scanning calorimetry, X-ray powder diffraction, and FT-IR analysis were applied. The melting point (T _m) was 177.4 °C (450.6 K), and T _g was determined to be 88.9 °C (362.1 K). The quotient T _g/T _m was 0.80, and this API was therefore classified as a good glass former.