Synthesis of vinca alkaloids and related compounds part 94. Epimerization of compounds with aspidospermane and D‐secoaspidospermane skeleton

The individual epimerization steps of vincadifformine ( 1 ), deethylvincadifformine isomers ( 2,3 ), their synthetic intermediates ( 4–13 ) as well as that of simpler compounds with D‐secoaspidospermane skeleton ( 15–17 ) were studied a ) in protic medium (boiling deuteroacetic acidic) and b ) under reductive (with sodium borodeuteride in boiling acetic acid, or with sodium borohydride in boiling deuteroacetic acid) conditions.     

LC-UV Assay of Tolperisone HCl from Sustained Release Matrix Tablets

Tolperisone HCl is a central muscle relaxant, which was incorporated in a matrix system formulated with poly(ethylene oxide)–PEO, in order to achieve adequate gastric residence time. This tablet presents considerable analytical difficulties in the quantitative determination of the drug, because the PEO matrix causes significant increase of viscosity in the samples. Our purpose was to develop a reproducible sample preparation method, which is adapted from parameters of the in vitro dissolution test and validate an LC-UV analytical method, which allows good recovery of the drug (99.97%). The developed analytical method was suitable for quantitative analysis of tolperisone HCl in matrix tablets.     

All regular Landsberg metrics are Berwald

This article negatively answers the long standing problem concerning the existence of non-Berwald Landsberg metrics.     

New chiral catalysts: synthesis and fragmentation pattern of C9-o-silanized cinchonidines

Summary We synthesized C9-O-silyl ethers of cinchonidine and dihydrocinchonidine (1-8), seven of which have not been known before. The structures of the compounds were verified by ESI-ion-trap MS and ¹H-NMR. Fragmentation of silyl ethers containing Si-phenyl bonds was studied for the first time. The compounds obtained will be utilized as chiral catalysts of certain asymmetric syntheses.</o:p>     

Nash equilibria in random games

We consider Nash equilibria in 2‐player random games and analyze a simple Las Vegas algorithm for finding an equilibrium. The algorithm is combinatorial and always finds a Nash equilibrium; on m × n payoff matrices, it runs in time O(m²nloglog n + n²mloglog m) with high probability. Our result follows from showing that a 2‐player random game has a Nash equilibrium with supports of size two with high probability, at least 1 − O(1/log n). Our main tool is a polytope formulation of equilibria. © 2007 Wiley Periodicals, Inc. Random Struct. Alg., 2007     

Robust UHPLC Separation Method Development for Multi-API Product Containing Amlodipine and Bisoprolol: The Impact of Column Selection

This paper describes a new and fast ultra-high pressure liquid chromatographic separation of amlodipine and bisoprolol and all their closely related compounds, for impurity profiling purposes. Computer-assisted method development was applied and the impact of several state-of-the-art stationary phase column chemistries (50 × 2.1 mm, sub-2 μm, and core–shell type materials) on the achievable selectivity and resolution was investigated. The work was performed according to quality by design principles using design of experiment with three experimental factors; namely the gradient time (t _G), temperature (T), and mobile phase pH. Thanks to modeling software, it was proved that the separation of all compounds was feasible on numerous column chemistries within <10 min, by proper adjustments of variables. It was also demonstrated that the reliability of predictions was good, as the predicted retention times and resolutions were in good agreement with the experimental ones. The final, optimized method separates 16 peaks related to amlodipine and bisoprolol within 7 min, ensuring baseline resolution between all peak-pairs.     

Lanthanide dota-like complexes containing a picolinate pendant: structural entry for the design of Ln(III)-based luminescent probes

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ? Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.