New routes to clavine-type ergot alkaloids. Part 2: Synthesis of the last, so far not yet synthesized member of the clavine alkaloid family, (±)-cycloclavine

Starting from 4-bromo-Uhle's ketone (2), an alkylation step using ethyl 3-methylamino-propionate followed by intramolecular aldol condensation in two steps, transformation of the ester group into a methyl group, and finally cyclopropanation of the 8,9 double bond, resulted in a six-step total synthesis of (±)-cycloclavine (1).     

The Synthesis of Pamidronic Derivatives in Different Solvents: An Optimization and a Mechanistic Study

The synthesis of pamidronic acid and sodium pamidronate dihydrate from β‐alanine and P‐reagents (phosphorus trichloride and phosphorous acid) was investigated at 75°C in different solvents, and the preparation was optimized. In sulfolane, the use of 2 equiv of phosphorus trichloride and phosphorous acid was found the optimum to lead to pamidronic acid in a yield of 63%. In methanesulfonic acid, 3.2 equiv of phosphorus trichloride was necessary without any phosphorous acid to give pamidronate dihydrate in the best yield (57%) after hydrolysis and pH adjustment. In the first case, the P‐nucleophile may be (HO)₂P–O–PCl–O–P(OH)₂ or (HO)₂P–O–PCl₂, whereas in the second case, the P‐reactant is probable Cl₂P–O–S(O)₂Me. It can be said that the mechanism proposed for the formation of pamidronic acid is highly influenced by the solvent used, as it determines the necessary P‐reagent(s). Our results promote the “on purpose” planning of the synthesis of dronates.     

Localization under the effect of randomly distributed decoherence

Electron transport through disordered quasi one-dimensional quantum systems is studied. Decoherence is taken into account by a spatial distribution of virtual reservoirs, which represent local interactions of the conduction electrons with their environment. We show that the decoherence distribution has observable effects on the transport. If the decoherence reservoirs are distributed randomly without spatial correlations, a minimal degree of decoherence is necessary to obtain Ohmic conduction. Below this threshold the system is localized and thus, a decoherence driven metal-insulator transition is found. In contrast, for homogenously distributed decoherence, any finite degree of decoherence is sufficient to destroy localization. Thus, the presence or absence of localization in a disordered one-dimensional system may give important insight about how the electron phase is randomized.     

A novel ambident reactivity of azolylacroleins

Reaction of azolylacroleins with phosphoranes bearing a conjugated double bond was found to yield either azolyltrienes in a Wittig reaction, or to undergo cyclization to a dihydrobenzene containing the azole substituent. Transformation with an aza-Wittig reagent gave tetrazolylpyridines. The ambident reactivity was found to be dependent on the substituent of the phosphorane, which was rationalized by ab initio (DFT) calculation of the atomic charges of the reaction centres.     

Investigation of the crystallinity of sugar alcohols co-ground with polymeric excipients

Particle size reducing methods demand high energy input, so during these procedures crystallinity change always can occur. These changes can be enhanced by additives, which are often used to improve the dissolution, the powder rheological properties or the processability of the API (active pharmaceutical ingredient), or to support the particle size reduction. Different materials act differently during these crystallinity changing methods: some materials are easy to amorphize, while some of them can be really resistant. In this work, two chemically equivalent sugar alcohols as model materials—β-d-mannitol as poor glass former and d-sorbitol as good glass former—were chosen to be co-ground with polymeric additives (PVP C30 and PEG 6000). During the 120 min milling process mannitol showed just minor change in crystallinity alone or with PEG. But milled with PVP some amorphization was found. Sorbitol suffered noteworthy changes in crystallinity: raw sorbitol lost its crystallinity during the milling, and also polymorphic transition was displayed. Same transition happened during the milling with PVP: the whole crystallinity of the sorbitol decreased, while the amount of gamma polymorph increased. During the co-grinding with PEG, the polymer prevented the amorphization of sorbitol and kept the well-ordered crystal structure of the material.     

Effect of sample preparation methods on the D,L-enantiomer ratio of extracted selenomethionine

Effects of the two most widespread sample preparation techniques on the d,l-enantiomer ratio of extracted selenomethionine were monitored through the analysis of the certified reference material selenium-enriched yeast and the isolated protein fraction of high selenium monkeypot nut. The extracted selenomethionine (SeMet) fractions were orthogonally cleaned up with anion exchange chromatography before carrying out the enantiomer-specific detection to increase the robustness and the efficiency of the subsequent o-phthal-aldehyde and n-isobutyril-cysteine-based derivatisation process and reversed phase-high-performance liquid chromatography-inductively coupled plasma mass spectroscopy (ICP-MS) detection. The two techniques, namely methanesulphonic acid (MSA) based digestion and proteolytic digestion with protease XIV, resulted in significantly different ratio of d,l-selenomethionine with the final results of 2.2–2.7% and 0.5–0.6% of d-SeMet, respectively. The study revealed significant differences in the ICP-MS-related sensitivity of the derivatised selenomethionine enantiomers, which calls attention to the quantification of this selenoamino acid after MSA hydrolysis.     

Extension of the invariant environment refinement technique + reverse Monte Carlo method of structural modelling for interpreting experimental structure factors: the cases of amorphous silicon, phosphorus, and liquid argon

The invariant environment refinement technique, as applied to reverse Monte Carlo modelling [invariant environment refinement technique + reverse Monte Carlo (INVERT + RMC); M. J. Cliffe, M. T. Dove, D. A. Drabold, and A. L. Goodwin, Phys. Rev. Lett. 104, 125501 (2010)], is extended so that it is now applicable for interpreting the structure factor (instead of the pair distribution function). The new algorithm, called the local invariance calculation, is presented by the examples of amorphous silicon, phosphorus, and liquid argon. As a measure of the effectiveness of the new algorithm, the ratio of exactly fourfold coordinated Si atoms was larger than obtained previously by the INVERT-RMC scheme.     

Synthetic procedure to pyrido[2,1-f][1,2,4]triazinium salt and related compounds

N-aminopyridyl ketone salts were reacted with formamide to yield heteroaromatic pyrido[2,1-f][1,2,4]triazinium salts. Upon storage of these products in the presence of water, formation of covalent hydrates have been observed. Reaction of the same starting compound with urethane yielded 3-chloropyrido[2,1-f][1,2,4]triazinium salt which readily reacted with secondary amines to afford 3-amino derivatives. An analogous ring closure reaction of 2-formylaminomethyl- and formaminobenzylpyridine allowed the synthesis of the partially reduced 3,4-dihydropyrido[2,1-f][1,2,4]triazinium compounds. The cyclization procedure was also applied for the synthesis of the related pyrimido[2,1-f][1,2,4]triazinium salt.     

Thermal properties of electrospun polyvinylpyrrolidone/titanium tetraisopropoxide composite nanofibers

Journal of Thermal Analysis and Calorimetry - In this work, polyvinylpyrrolidone/titanium tetraisopropoxide (PVP/TTIP) composite nanofibers were prepared by electrospinning from alcoholic...     

Comparison of the Thermal Desorption Spectra and Exoemission Spectra of BeO:TiO2 and BeO:Li Thermally Stimulated Exoelectron Emission Detectors

In thermally stimulated exoelectron emission (TSEE) dosimetry the irradiation is generally executed in air while the read out is in methane. Under these conditions adsorption/desorption effects appear which influence the exoemission. BeO:Li and BeO:TiO₂ ceramics were compared from this point of view. The effect of adsorption/desorption was studied in such a way that in the cycles of irradiation/read-out the cooling down was executed successively in a methane atmosphere or in air. The TSEE curves of the BeO:TiO₂ ceramic were more influenced by the cooling atmosphere than those of the BeO:Li ceramic. In order to explain this result the thermal desorption spectra of these materials was taken. © 1997 John Wiley & Sons, Ltd.