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(8 hours) Advanced methodologies in organic chemistry |
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Teacher Andrea Calcaterra |
Learning outcomes
These lessons aim covering the basic principles and the recent advances in the main branches of organic chemistry: (1) metal-assisted cross-coupling reactions, (2) asymmetric organocatalysis, (3) green chemistry and (4) retrosynthetic analysis. This cycle of lessons talks about the application of these fields useful for large-scale (bulk) and smaller-scale (fine chemicals) production as well the synthesis of natural and bioactive compounds.
Syllabus
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Fundamental aspects in organic synthesis: metal-assisted cross-coupling reactions, asymmetric organocatalysis, green chemistry, retrosynthetic analysis.
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Key reactions in organometallic chemistry such as transmetalation, oxidative addition, and reductive elimination as well as the role of different types of ligands will be discussed. Recent advances of Negishi, Stille, Suzuki, Sonogashira and Buchwald-Hartwig reactions will be described.Principle of organocatalysis, amino and amino-derivatized catalysis in the asymmetric synthesis and related reaction mechanisms. Recent advances of imino/enamine catalytic reactions and hydrogen bonding mediated reactions.
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Selected principles of green chemistry, prevention of waste; development of atom economy; design and development of safe chemicals; usage of safe solvents and auxiliary substances. Use of catalytic reagents in organic synthesis: examples and applications of homogenous and heterogeneous catalysts in the preparation of bioactive compounds. Biocatalysts.
Retrosynthetic analysis. Synthons and reagents. Group disconnections. Regio- and chemoselectivity. Useful reactions in total synthesis. Control of stereochemistry. Selected total synthesis. |
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(2 hours) Advanced methodologies in organic chemistry: Case studies |
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Teacher Antonella Goggiamani |
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The synthesis of nitrogen-fused polycyclic compounds has gained significant attention due to their diverse applications in pharmaceuticals and material science. Among the most efficient methods for constructing these structures are the copper-catalyzed 1,3-dipolar cycloaddition of organic azides and terminal alkynes (CuAAC) and direct C-H bond functionalization. CuAAC, often celebrated as a cornerstone of click chemistry, is renowned for its high efficiency, regiospecificity, and eco-friendly attributes, such as producing minimal waste and requiring fewer resources. Similarly, C-H bond activation allows for direct functionalization of otherwise inert bonds, enabling streamlined synthesis of complex heterocyclic frameworks. These approaches are particularly advantageous for synthesizing hybrid compounds incorporating quinoline, pyrroloquinoline, dihydroquinoline, and benzodiazepine motifs fused with triazole moieties. This lesson will explore the mechanistic underpinnings, sustainability benefits, and practical applications of these techniques, emphasizing their roles in accessing structurally diverse, nitrogen-rich heterocycles with enhanced efficiency and reduced environmental impact. |
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(2 hours) Advanced methodologies in organic chemistry: Case studies |
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Teacher Giancarlo Fabrizi |
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The synthesis of indole derivatives via palladium-catalyzed reactions of propargylic compounds represents a highly versatile and efficient approach in organic chemistry. Propargylic compounds serve as key intermediates due to their ability to undergo diverse transformations under palladium catalysis, including cyclization reactions that facilitate the construction of both carbocyclic and heterocyclic systems. Notably, ethyl 3-(o-trifluoroacetamidoaryl)-1-propargylic carbonates, containing a nitrogen nucleophile in proximity to the propargylic moiety, are particularly valuable for synthesizing 2-substituted indoles. These intermediates allow for precise control over the substitution pattern by employing various external nucleophiles, such as amines, hydrides, soft carbanions, or boronic acids. This strategy offers significant flexibility in tailoring the structure of indole derivatives, which are widely recognized for their biological relevance and applications in pharmaceuticals. The lesson will delve into the mechanistic insights and practical utility of these palladium-catalyzed reactions in modern synthetic methodologies. |
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(8 hours) Advanced Mass spectrometry for structural elucidation |
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Teacher Davide Corinti |
Learning outcomes
Main goals of this course are:
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To provide an introduction to mass spectrometry and its hyphenated techniques (Ion Mobility, MALDI imaging, CID, UVPD, etc.).
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To demonstrate and discuss applications of MS and related techniques in biological, pharmaceutical and food chemistry.
At the end of the course, students should be able to:
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Understand the basic concepts of mass spectrometry and related techniques.
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Demonstrate an understanding of how and why mass spectrometry can be applied to life sciences;
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Critically assess current literature on mass spectrometry analyses.
Syllabus
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Introduction to mass spectrometry.
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Ion sources (ESI, APCI, MALDI, APPI) and their application in life sciences.
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Ion activation methods (CID, UVPD, IRPD, EXD) with examples Ion mobility-MS and its use for complex biological matrices and native mass spectrometry of biomolecular ions.
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MALDI imaging for clinical diagnosis and analysis of biological tissues.
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(2 hours) Advanced Mass spectrometry for structural elucidation: Case studies |
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Teacher Barbara Chiavarino |
The aim of this seminar is to provide an in-depth understanding of the application of infrared multiple photon dissociation (IRMPD) action spectroscopy, a powerful tool used to probe vibrational modes – and, by extension, gain structural insights – of an ion or an ion-molecule complex, mass-isolated within an ion trap mass spectrometer. The fundamentals and instrumentation of IRMPD spectroscopy will be briefly illustrated.
A significant part of the module will be dedicated to presenting an overview of the results, applications and usefulness of IRMPD technique. We will examine how IRMPD action spectroscopy can be used to obtain valuable structural information on ions of fundamental, biological, and pharmaceutical importance. Recent advancements in its application to mass spectrometry-based metabolomics analysis will also be explored. |
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(8 hours) Advanced analytical techniques for structural elucidation |
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Teacher Giulia Mazzoccanti |
Learning outcomes
This course is designed to provide participants with a comprehensive understanding of separation science:
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Gain in-depth knowledge of advanced separation techniques, with a focus on ultra-high-performance chromatography (UHPC) and explore the meaning of chromatographic parameters. Understand the thermodynamic significance of the retention factor and selectivity and delve into the concept of kinetics in chromatography.
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Acquire specialized skills in separating chiral molecules, understanding the principles and applications of chiral chromatography, and exploring advanced methods for resolving enantiomers.
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Explore techniques specific to the separation of (bio)pharmaceuticals, including protein and peptides. Investigate the challenges associated with detecting impurities in therapeutic peptides, especially considering minimal modifications, such as epimers, which pose challenges in both molecular structure and isobaric nature.
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Understand advanced multidimensional liquid chromatography (such as bidimensional chromatography 2D-LC) techniques tailored for the analysis of complex mixtures. Delve into the synergistic benefits of coupling different separation dimensions.
Syllabus
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Introduction to Ultra-High-Performance Chromatography (UHPC).
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Understanding the Thermodynamics of Retention Factor and Selectivity.
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Introduction to Chromatographic Kinetics (Efficiency).
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Principles and Applications of Chiral Chromatography.
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Techniques for Separating Chiral Molecules.
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Advanced Methods for Resolving Enantiomers.
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Specific Techniques for Separating Proteins and Peptides.
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Challenges in Detecting Impurities in Therapeutic Peptides (e.g., epimers).
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Introduction to Multidimensional Liquid Chromatography.
In-depth Exploration of Bidimensional Chromatography (2D-LC). |
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(2 hours) Advanced analytical techniques for structural elucidation: Case studies |
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Teacher Alessia Ciogli |
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Dynamic high/ultra-high performance liquid chromatography (D-HPLC and D-UHPLC) on enantioselective stationary phases represents a well-established technique to investigate chiral molecules with internal motions that result in stereoinversion (trough stereogenic centers, axes and their combination). Two requirements are necessary to identify configurational and/or conformational stereoisomers by D-HPLC: i) selectivity of the stationary phase towards the investigated compounds and ii) stereoinversion process occurring at the time scale of the separation. Kinetic parameters for the on-column interconversion phenomena can be extracted from experimental peak profiles by computer simulation or by direct calculation methods. The technique has been used in a wide range of temperatures and it is complementary to the off-column racemization experiments and to the dynamic NMR spectroscopy. Basic principles on enantioselective HPLC and D-HPLC will be presented together with the selected examples of interest in organic and medicinal chemistry. |
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(2 hours) Metabolomic analysis in food science: Case studies |
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Teacher Luisa Mannina |
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The aim of this course is to provide an in-depth understanding of the application of NMR-based metabolomics in the study of biological fluids to identify specific diseases and assess the impact of particular dietary regimes. Key aspects of both the NMR methodology and chemometric techniques will be thoroughly explored. Various practical applications will be presented, allowing students to become familiar with the NMR spectra of biological fluids such as urine and saliva, as well as the different methods used to analyze metabolites. Additionally, students will gain the ability to critically assess and select the most appropriate chemometric approach based on the specific research problem. |
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(2 hours) Metabolomic analysis in food science: Case studies |
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Teacher Cinzia Ingallina |
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This seminar will delve into the application of metabolomics in the study of natural products, with a particular focus on Traditional Chinese Medicine (TCM) and Mediterranean officinal plants (MOP). Metabolomic techniques, including fingerprinting and profiling, have transformed the analysis of complex plant mixtures, offering quantitative insights into specific compounds found in TCM formulations. The discussion will spotlight research on notable medicinal plants such as Angelica sinensis and Panax ginseng from TCM, as well as Melissa officinalis, Taraxacum officinale, and Arctium lappa among the MOP. By harnessing these advanced methodologies, researchers have identified several beneficial compounds for human health, including an anticancer saponin, thereby demonstrating the potential of metabolomics to reveal bioactive compounds. The seminar will emphasize how this approach bridges traditional knowledge with modern science, facilitating advancements in drug discovery, food chemistry, and natural product innovation. |
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(8 hours) Biochemical aspects of nutrition |
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Teacher Anna Maria Giusti |
Learning outcomes
This course aims to understand the factors that influence food quality and define appropriate parameters for evaluating food quality. It will explore the impact of food processing, particularly thermal treatments, on phytochemicals. Furthermore, the course will delve into the application of photoacoustic techniques for non-destructive analysis of phytochemicals in plant foods. Finally, it will compare the results of destructive and non-destructive analytical methods.
Syllabus
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Food total quality definition.
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Markers of food quality.
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Importance of phytochemicals as markers for food quality definition.
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Effect of thermal treatment on phytochemicals in some plant foods.
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Photoacoustic technique as non-destructive analytical approach to detect bioactive. Compounds in plant foods.
Comparison of results obtained between destructive and non-destructive techniques. |