Enantioselective Chromatography: an Essential and Versatile Tool for the Analytical and Preparative Separation of Enantiomers

Chromatography on chiral stationary phases and electrophoresis in the presence of chiral selectors have become essential tools for the determination of enantiomeric purity in connection with synthesis and with biological studies of chiral molecules. Moreover, the chromatographic resolution of racemates on a preparative scale compels increasing recognition as alternative to 'preparing' pure enantiomers. The state-of-the-art of enantioselective chromatography in the analytical and preparative field is reviewed with particular emphasis on the achievements carried out in Switzerland

New Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors

In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro- substituted alkyl chains at the 4-position of the thiadiazine ring in an attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and a marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at the 4-position of benzothiadiazine dioxides on activity and metabolic stability

Autonomous space exploration using the Turtlebot mobile platform

Cilj diplomske naloge je implementacija avtonomnega raziskovanja prostora na mobilni platformi Turtlebot, ki uporablja razvojno okolje ROS. Implementirali smo raziskovalni algoritem, ki temelji na zaznavi obrobij in njihovi uporabi kot potencialnih raziskovalnih ciljev. Ker pa lahko algoritem pri izbiri raziskovalnih ciljev upošteva različne kombinacije ocen raziskovanja, smo nato preizkušali in primerjali, katera kombinacija ocen omogoča najbolj učinkovito raziskovanje prostora. Različne strategije izbire raziskovalnih ciljev smo ocenjevali in primerjali na podlagi štirih kriterijev ter referenčne strategije, ki naključno izbira raziskovalne cilje. Podatke za primerjavo smo dobili tako, da smo za vsako strategijo opravili deset uspešnih raziskovanj. Te smo nato kot skupine povprečnih vrednosti in odstopanj primerjali med seboj na podlagi referenčne strategije in kriterijev. Implementirali smo modul, ki poleg raziskanosti prostora in časa raziskovanja omogoča tudi beleženje zgodovine premikov in s tem pot raziskovanja, ki jo opravi Turtlebot.The purpose of this undergraduate thesis is to implement the autonomous exploration of space on the Turtlebot mobile platform that uses the ROS development environment. We implemented an exploration algorithm based on the detection and use of frontier regions as potential exploration goals. Since the algorithm is able to choose an exploration goal based on the combination of different assessments, we tested and compared which combination of goal assessments enables the most efficient exploration of a given space. We assessed and compared different strategies of goal setting on the basis of four criteria and a referential strategy which selects its exploration goals randomly. In order to get the data necessary for comparison, we conducted ten successful explorations per strategy and compared them on the basis of the referential strategy and criteria. We implemented our own module, which tracks the amount of space explored and the time spent for exploration, while also documenting the path traveled by the Turtlebot during exploration

Enantioselective Chromatography: From its Emergence to its Successful Implementation in the Pharmaceutical Environment

The author describes the emergence and development of enantioselective chromatography as a powerful tool for the separation of stereoisomers, on analytical, preparative, and production scale. He summarizes his early contribution to the advance and propagation of this particular technology at the interface between chemistry, separation sciences, and physics, going back to his growing interest in chirality which was stimulated by a postdoctoral stay at the university of Genev

Practical Advances in SFC for the Purification of Pharmaceutical Molecules

Recent progress in supercritical fluid chromatography (SFC) instrumentation has led to renewed interest in the technique as a powerful tool for chiral and achiral separations of pharmaceutical molecules, for both analytical and preparative purposes. The “green” aspect of the technique and low running costs make SFC technology particularly attractive for preparative chromatography because it considerably reduces the consumption of organic solvents. These factors led to a revised strategy for purification and to a general interest in evaluating possible extensions for the application of packed SFC (pSFC). The results of this extensive evaluation have led to the establishment of SFC platforms for preparative achiral purifications as a standard practice, alongside its use for preparative chiral separations

Polysaccharide Derivatives as Unique Chiral Selectors for Enantioselective Chromatography

From the beginning of the 1980s, the life science industry increasingly recognized the importance of chirality in biological interaction processes, but the methods for preparing optically pure drugs were still limited. Most of the syntheses of chiral compounds were performed starting from optically active building blocks (chiral pool), mainly from natural sources, or by resolution of the enantiomers via formation of diastereomers. In this context, there was a growing interest for enantioselective processes, such as synthetic methodologies and separation techniques for accessing optically pure substances in an effective manner. Among the separation approaches, enantioselective chromatography looked very promising and a project aiming to explore this option was started in the Central Research Laboratories of former Ciba-Geigy. This article reviews the story of this development which culminated in the discovery of highly efficient polysaccharide-based chiral stationary phases which have now become the gold standard in the world of enantioselective chromatography. It shows also how the technique of enantioselective chromatography has evolved from an analytical tool to a practical preparative technology, up to production scale

Photochemically Immobilized 4-Methylbenzoyl Cellulose as a Powerful Chiral Stationary Phase for Enantioselective Chromatography

A process to immobilize para-methylbenzoyl cellulose (PMBC) on silica gel has been developed and applied to prepare chiral stationary phases (CSPs) for enantioselective chromatography. The immobilization was achieved by simple irradiation of the polysaccharide derivative with ultraviolet light after coating on a silica gel support. The influence of parameters such as irradiation time and solvent on immobilization effectiveness were investigated. The performance of the prepared immobilized phases were evaluated by injection of a series of racemic compounds onto the packed columns and determination of their chiral recognition ability. By contrast to the classical coated phase, the immobilized CSP can be used under various chromatographic conditions without limitation of organic solvent types as the mobile phase. This extended applicability permits to improve selectivity and to resolve chiral compounds which are not or only poorly soluble in the mobile phases which are compatible with the non-immobilized PMBC stationary phase