You are here: Home > Study > PhDs and Professional Masters programmes, Specialisations and advanced training > Course unit catalogue > Experimental Methodologies for the Preparation of Drugs (Gr. B) 2023/2024

37722 - Experimental Methodologies for the Preparation of Drugs (Gr. B)

Academic Year 2023/2024

Learning outcomes

At the end of the course, which also includes laboratory exercises, the student knows: the basic concepts related to synthetic and extraction strategies used in research and industrial laboratories for the discovery and development of new drugs; the classical and innovative methodologies for the synthesis of low molecular weight molecules having biological activity and for the extraction of products of natural origin. Moreover the student learns to face an experimental procedure for the synthesis, the extraction and the characterization of a single compound, to consult the scientific literature before the experiment and to report the experimental results obtained.

Course contents

Teoretical lessons

MODULE 1

Safety concepts in the chemical laboratory. Techniques and apparatus: glassware, equipment with interchangeable joints in general use in preparative organic chemistry: care and maintenance. Cooling and heating of reaction mixtures. Methods of stirring.
Isolation and purification techniques: Purification of solids. Decolorization. Gravity and vacuum filtration: depth and surface filters. Crystallization, reprecipitation. Chromatographic techniques, adsorption chromatography: thin layer chromatography, silica gel column chromatography, flash column chromatography. Synthesis of molecule libraries, combinatorial chemistry, solid phase synthesis. Protocol for laboratory notebook. Reactions involving water formation and use of Dean Stark Trap. Microwave-assisted reactions. Reactions conducted under special conditions.
Wittig reaction and synthesis of 9-(2-phenylethenyl)anthracene. Hantzsch reaction and synthesis of nifedipine. Acetylation reaction and synthesis of acetylsalicylic acid. Pabon reaction and synthesis of curcumin. Aldolic condensation and synthesis of a chalcone library. Esterification reaction and synthesis of methyl benzoate. Nucleophilic substitution reaction and synthesis of 4-(4-methoxyphenoxy)benzaldehyde. Synthesis of a library of phenylhydrazones. Grignard reaction. Reducing agents and Reduction Reactions. 

MODULE 2

Green and sustainable manufacturing concepts in the pharmaceutical industry. Green approaches for API production.

MODULE 3

Theory of extraction.
Classification of extracts.
Solvent extractions. Ternary diagram. Extraction coefficient, distribution coefficient. Acid-liquid-liquid base extraction. Countercurrent extraction. Extraction with liquid ions and with eutectic mixtures. Extraction with two-phase aqueous systems based on ionic liquids. Continuous solid-liquid extraction (soxhlet). Solid-phase extraction. Accelerated extraction with pressurized solvents. Extraction with supercritical fluids. Extraction with ultrasound. Microwave-assisted extraction. Drying of solids, drying of apparatus. Anhydrous reactions. Drying of liquids and solutions of organic compounds in organic solvents: drying agents. Distillation. Rotary evaporator. Steam current distillation. Fractional distillation: at atmospheric and reduced pressure. 

Laboratory experiences

MODULE 4

Synthesis, purification and structural characterization of small molecules.
Wittig reaction and synthesis of 9-(2-phenylethenyl)anthracene.
Hantzsch reaction and synthesis of nifedipine.
Acetylation reaction and synthesis of acetylsalicylic acid.
Claisen-Schmidt condensation and synthesis of a library of chalcones.
Fisher esterification reaction and synthesis of methyl benzoate.
Pabon's reaction and synthesis of curcumin.
Nucleophilic substitution reaction and synthesis of 4-(4-methoxyphenoxy)benzaldehyde.
Synthesis of a library of phenylhydrazones.

MODULE 5

Microwave assisted reactions: green synthesis of aspirin. Enzymatic reduction of ethyl acetoacetate.

MODULE 6

Extraction, purification and structural characterization of small molecules from plant matrices.
Lycopene and beta-carotene from Lycospericon esculentum.
Trimyristin from Myristica fragrans.
Flavonoids and essential oil from Matricaria camomillae.
Nicotine from Nicotiniana tabaccum.
Xanthine alkaloids from Thea sinensis.
Curcuminoids from Curcuma longa.

Readings/Bibliography

1) VOGEL. CHIMICA ORGANICA PRATICA. CASA EDITRICE AMBROSIANA, SECONDA EDIZIONE, MILANO 1988 2) R. M. ROBERTS, J.C. GILBERT, S. F. MARTIN. CHIMICA ORGANICA SPERIMENTALE. ZANICHELLI, BOLOGNA 2003 3) A.J. HANDELY. EXTRACTION METHODS IN ORGANIC ANALYSIS. SHEFFIELD ACADEMIC PRESS, CANADA 1999 4) D.L. PAVIA, G. M. LAMPMAN, G.S. KRIZ. IL LABORATORIO DI CHIMICA ORGANICA, EDIZIONI SORBONA , MILANO 1994 5) P.M. DEWICK. CHIMICA, BIOSINTESI E BIOATTIVITA' DELLE SOSTANZE NATURALI. PICCIN, PADOVA 2000 6) MARCO D'ISCHIA LA CHIMICA ORGANICA IN LABORATORIO PICCIN PADOVA 2002 LUCIDI, CD, APPUNTI DI LEZIONI, COPIE DI ARTICOLI INERENTI GLI ARGOMENTI DI LEZIONE ADVANCED PRATICAL ORGANIC CHEMISTRY THIRD EDITION LEONARD LYGO PROCTER CRC PRESS

Teaching methods

The course includes an individual laboratory practice aimed to furnish to the students the skills for applying different methods for the synthesis of small molecules and the preparation of plant extracts, theoretically explained during lectures.

Assessment methods

The final examination will be aimed at ascertaining the achievements of the following skills: knowledge of the basic concepts regarding the synthetic strategies and the related laboratory processes for the discovery and development of new drugs employed in research and industry laboratories; knowledge of the essential aspects of practical pharmaceutical chemistry techniques along with classical and innovative methodologies for the synthesis of biologically active small molecules; knowledge of the methodologies for the extraction for natural products.

Dates for the three modules are fixed in a single day. Moreover, for the examination an online appointment through AlmaEsami: https://almaesami.unibo.it/almaesami/welcome.htm . is mandatory. The oral exam for each module should be taken according to the fixed dates, even on different dates. The order of oral tests can be chosen by the student.

The learning assessment is carried out through a) a practical laboratory exam, carried out at the end of the laboratory practice , b) and an oral examination.

In detail: a) the practical exam (foreseen for module 4) with unlimited validity, is preliminary to the oral examination and consists in performing a synthesis (MODULE 4) selected from those already performed during the practical laboratory course, accompanied by from a final report. b) The oral exam consists of specific questions on topics dealt with during the Course and is organized as follows:

MODULE 1: the student will be asked two questions. The first will relate to a laboratory experience (it will take inspiration from the laboratory notebook that the students question will have compiled describing and commenting on the lab experiences); the second one, aimed at assessing the level acquisition of the expected skills, will concern theoretical and instrumental aspects underlying the laboratory experiences.

MODULE 2: the oral exam consists of a discussion of a scientific article chosen by the student, concerning the topics covered during the course.

MODULE 3: the oral exam consists of an interview on a written thesis concerning a topic covered during the course.

The final grade of the whole Course will be the weighted average of the marks obtained in the individual modules and will take into account the results of the practical laboratory test.

Students to whom the Council validates the frequency signature acquired in the previous career must pass the practical laboratory test before taking the oral exam.

Teaching tools

Video projector-PC system, laboratory for the practical exercises. The slides presented during the lectures are made available to students on the online teaching platform (Virtuale), username and password are reserved only for Bologna University students.

Office hours

See the website of Federica Belluti

See the website of Elisa Uliassi

See the website of Elisa Uliassi