1,720,970 research outputs found
Greening Cannabinoids Purification Through Advanced Multicolumn Preparative Chromatography Methods
No full textLa crescente domanda di tecnologie sostenibili per la purificazione dei cannabinoidi ha spinto lo sviluppo di metodi avanzati che bilanciano l'efficienza con la riduzione dell'impatto ambientale. Questa tesi affronta queste sfide proponendo l'implementazione di processi cromatografici innovativi basati sulle tecniche di Alternative Pump Recycling (APR) e Simulated Moving Bed (SMB), con un focus sull'uso di solventi green come l'etanolo. L'obiettivo è migliorare la separazione di composti bioattivi della Cannabis come il cannabidiol (CBD) e il tetraidrocannabinolo (THC), garantendo al contempo una significativa riduzione del consumo di solventi, dei rifiuti generati e dei costi energetici. Nella prima parte del lavoro, viene esplorato l'APR, utilizzando l'etanolo come fase mobile per la rimozione del THC da matrici ricche di CBD. Grazie all'uso combinato di simulazioni numeriche e sperimentazioni pratiche, l'APR ha dimostrato di raggiungere elevati livelli di purezza e recupero del CBD, garantendo una separazione efficace anche in condizioni critiche di co-eluzione. Le simulazioni basate su modelli matematici hanno ottimizzato il processo, riducendo il tempo e le risorse necessarie. I risultati mostrano che la tecnica è comparabile o superiore alla cromatografia tradizionale in termini di prestazioni. Nella seconda parte, la tesi si concentra sull'applicazione della tecnologia SMB, considerata una delle tecniche più efficienti per separazioni continue su scala industriale. Sono stati adottati due approcci distinti: il primo utilizza la cromatografia in fase normale (NP) per la purificazione del cannabigerolo (CBG), sfruttando una combinazione di esano ed etanolo per garantire elevate capacità di carico e separazioni efficienti. Il secondo approccio, operante in fase inversa (RP), ha impiegato una miscela di etanolo e acqua per l'eliminazione completa del THC da matrici complesse, rendendo il processo adatto a rigorosi standard normativi ed ecologici. In entrambi i casi, il sistema SMB ha mostrato vantaggi significativi rispetto alle tecniche tradizionali, in termini di consumo di solventi e un aumento della produttività. Infine, la tesi esplora la separazione chirale dei cannabinoidi, analizzando il comportamento di sei cannabinoidi su nove fasi stazionarie chirali derivate da polisaccaridi, sia in condizioni di NP che di RP. I risultati hanno rivelato distinti meccanismi di interazione in base alla configurazione della fase stazionaria, offrendo preziose informazioni per ottimizzare le separazioni enantiomeriche e per caratterizzare nuovi composti bioattivi. L'intero studio enfatizza l'importanza di combinare tecnologie innovative, approcci numerici e metodologie sostenibili per soddisfare le crescenti esigenze dell'industria dei cannabinoidi. Le tecniche sviluppate in questa tesi rappresentano un passo importante verso l'adozione di pratiche più ecologiche, mantenendo al contempo elevati standard di qualità e prestazioni. Questa ricerca non solo contribuisce a migliorare le operazioni industriali di purificazione, ma apre anche nuove opportunità per la produzione di standard analitici e per l'esplorazione dei cannabinoidi con potenziali applicazioni terapeutiche.The growing demand for sustainable technologies for cannabinoid purification has driven the development of advanced methods that balance efficiency and reduced environmental impact. This thesis confronts these challenges by proposing the implementation of innovative multicromatographic processes based on Alternative Pump Recycling (APR) and Simulated Moving Bed (SMB) techniques, with a focus on the use of green solvents such as ethanol. The goal is to improve the separation of bioactive compounds such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), while ensuring a significant reduction in solvent consumption, waste generated and energy costs. In the first part of the paper, APR is explored, using ethanol as the mobile phase for the removal of THC from CBD-rich matrices. Through the combined use of numerical simulations and practical experimentation, APR has been shown to achieve high levels of CBD purity and recovery, ensuring effective separation even under critical co-eluting conditions. Simulations based on mathematical models optimized the number of recycles, reducing the time and resources required for the process. Results show that the technique is comparable or superior to traditional batch chromatography in terms of performance. In the second part, the thesis focuses on the application of SMB technology, considered one of the most efficient techniques for continuous, industrial-scale separations. Two distinct approaches were taken: the first uses normal-phase (NP) chromatography for cannabigerol (CBG) purification, exploiting a combination of heptane and ethanol to ensure high loading capacities and efficient separation. The second approach, operating in reverse phase (RP), employed an ethanol-water mixture for complete THC depletion from complex matrices, making the process suitable for stringent regulatory and environmental standards. In both cases, the SMB system showed significant advantages over traditional techniques, with up to a 15 times reduction in solvent consumption and a 54% increase in productivity. Finally, the thesis explores the chiral separation of cannabinoids by analyzing the behavior of six compounds on nine chiral stationary phases derived from polysaccharides under both NP and RP conditions. The results revealed distinct interaction mechanisms based on stationary phase configuration, offering valuable insights for optimizing enantiomeric separations and characterizing novel bioactive compounds. The entire study emphasizes the importance of combining innovative technologies, numerical approaches, and sustainable methodologies to meet the growing needs of the cannabinoid industry. The techniques developed in this thesis represent an important step toward the adoption of more environmentally friendly practices while maintaining high standards of quality and performance. This research not only contributes to improved industrial purification operations but also opens new opportunities for the production of analytical standards and the exploration of cannabinoids with potential therapeutic applications
Effective and Practical Stereoselective Synthesis of Nutlins Precursors by Immobilization of Privileged Chiral Mono‐Amidine Catalyst
No full textA strategy for the immobilization of Johnston's Mono(AMidine) catalyst (MAM) onto polystyrene, silica and hybrid silica-polystyrene nanoparticles is presented. The catalyst activity was evaluated in the stereoselective aza-Henry reaction leading to the pivotal β-amino nitroalkane precursors of the anti-cancer agents Nutlins (with Nutlin-3a as the most active drug). The effect of the support and the linker on the catalytic performance was investigated, observing an interesting match/mismatch effect when using a chiral linker. The polystyrene-supported 3-pyrrolidinol-linked PS-(S)-Pyr-MAM organocatalyst showed the best activity among the tested catalysts, behaving very similarly to the homogeneous counterpart in the synthesis of a library of Nutlins precursors: yield up to 95%, ee up to 99%, and dr up to >99:1. The catalyst recyclability was also assessed through simple filtration, yielding a satisfactory 93% ee after 5 cycles, showing only a moderate decrease in conversion efficiency (c..
Recent developments in the high-throughput separation of biologically active chiral compounds via high performance liquid chromatography
No full textBioactive compounds, including active pharmaceutical ingredients (APIs), are often chiral molecules where stereoisomers have different biological and therapeutic activity. Nevertheless, the preparation of these molecules can lead to racemic or scalemic mixtures (it is not trivial to produce just the optically pure compound). The evaluation of the enantiomeric purity of bioactive compounds, and therefore quality, is indeed of fundamental importance for regulatory scopes. Chiral high performance liquid chromatography (HPLC) is the gold standard technique to separate and to purify enantiomers. This comes from the wide availability of commercial chiral stationary phases (CSPs) and operational modes, which makes the technique extremely versatile. In recent years, the most relevant trend in the field of chiral analytical HPLC has been the development of CSPs suitable for fast or even ultrafast separations, thus favoring the high throughput screening of biologically active chiral compounds. This process has somehow lagged behind compared to achiral HPLC, due to a series of practical and fundamental issues. The experience has shown how in chiral chromatography even very basic concepts, such as the supposed kinetic superiority of core-shell (pellicular) particles over fully porous ones to improve the chromatographic efficiency, cannot be taken for granted. In this review, the most relevant fundamental and practical features that must be taken into consideration to design successful high-throughput, fast enantioseparations will be discussed. Afterwards, the main classes of CSPs and the most relevant, recent (last five-year) high-throughput applications in the field of the separation of chiral bioactive compounds (for pharmaceutical, forensic, food, and omics applications) will be considered
Sustainable cannabinoids purification through twin-column recycling chromatography and green solvents
No full textIn the present study, twin-column recycling chromatography has been employed for the purification of a Cannabis extract by using a green solvent, ethanol, as the mobile phase. In particular, the complete removal of the psychoactive tetrahydrocannabinol (THC) from a Cannabis extract rich in cannabidiol (CBD) was achieved under continuous conditions. The performance of the method, in terms of compound purity, recovery, productivity and solvent consumption, was compared to that of traditional batch operations showing the potential of the twin-column recycling approach. The employment of a theoretical model to predict the band profiles of the two compounds during the recycling process has facilitated method development, thus further contributing to process sustainability by avoiding trial and error attempts or at least decreasing the number of steps significantly
Enzymatic Desymmetrisation of Prochiral <i>meso</i>-1,2-Disubstituted-1,2-Diaminoethane for the Synthesis of Key Enantioenriched (−)-Nutlin-3 Precursor
No full textHerein we present the biocatalysed preparation of a mono-N-carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of meso-1,2-disubstituted-1,2-diaminoethane using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl, diethyl and dimethyl carbonates. The reactions were conducted at different temperatures, for different reaction times and with variable co-solvent systems to evaluate the effects on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) when conducting the reaction solventless at 75 °C
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Recent developments and future perspectives of chiral liquid chromatography for food safety and quality
No full textFood products are important sources of both endogenous and exogenous chiral molecules, whose chiral distribution must be strictly controlled to ensure and preserve food quality and safety. Indeed, as an example, chiral pesticides are often administered as racemic mixtures to plants, and while one enantiomer is active, the other may have unknown effects on the human body and could potentially pose a danger to consumers.
Therefore, information about the chiral distribution of naturally occurring and artificially added compounds can help to assess food quality and traceability.
This work focuses on the most relevant findings and research in the field of chiral liquid chromatography to assess food safety and quality, following the success of previous reviews published on this topic. To avoid overlapping with previous reports, the analysis covers the last three years (2020–2023)
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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