87605 - Experimental Methodologies for the Preparation of Drugs (GrA)

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 notions in the chemical laboratory. Techniques and equipment: glassware, equipment with interchangeable joints of general purpose in preparative organic chemistry: care and maintenance. Cooling and heating of the reaction mixtures. Agitation methods. Isolation and purification techniques: solid compounds purification of. De-coloration. Gravity and vacuum filtration: depth filters and surface filters. Crystallization, re-precipitation. Chromatographic techniques: thin layer chromatography, silica gel column chromatography: flash column chromatography. Microwave-assisted reactions for pharmaceutical compounds synthesis. Combinatorial chemistry in drug development. Protocol for the laboratory notebook. Wittig reaction and synthesis of 9- (2-phenylethenyl) anthracene. Hantzsch reaction and nifedipine synthesis. Acetylation reaction and synthesis of acetylsalicylic acid. Pabon reaction and curcumin synthesis. Aldol condensation and synthesis of a chalcone library. Reaction of esterification and synthesis of methyl benzoate. Nucleophilic substitution reaction and synthesis of 4- (4-methoxyphenoxy) benzaldehyde. Synthesis of a phenylhydrazone library.

MODULE 2

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

MODULE 3

Extraction theory. Classification of extracts. Solvent extractions. Ternary diagram. Extraction coefficient, distribution coefficient. Liquid-liquid acid-base extraction. Extraction in countercurrent. Extraction with ions liquids and with eutectic mixtures. Extraction with two-phase aqueous systems based on ionic liquids. Continuous solid-liquid extraction (soxhlet). Solid phase extraction. Single and multiple cartridge systems. Solid phase microextraction. Speed up extraction by pressurized solvents. Extraction with supercritical fluids. Ultrasound-assisted extraction. Microwave-assisted extraction. Drying of solid compounds, drying of equipment. Anhydrous reactions. Drying of liquids organic compounds solutions in organic solvents: drying agents. Distillation. Rotary evaporator. Steam distillation. Atmospheric pressure and reduced pressure Fractionated distillation. Purification of the most common organic solvents.

Laboratory experiences

MODULE 4

Wittig reaction and synthesis of 9- (2-phenylethenyl) anthracene. Hantzsch reaction and nifedipine synthesis. Acetylation and synthesis reaction of acetylsalicylic acid. Pabon reaction and curcumin synthesis. Aldol condensation and synthesis of a calcone library. Reaction of esterification and synthesis of methyl benzoate. Nucleophilic substitution reaction and synthesis of 4- (4-methoxyphenoxy) benzaldehyde. Synthesis of a phenylhydrazone library

MODULE 5

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

MODULE 6

Purification by extraction of BOC-proline obtained by synthesis. Extraction, purification and quantitative determination of betacarotene from the Lycospericon esculentum. Extraction of trimirystin from Myristica fragrans. Extraction of flavonoids and essential oil from the dried flower heads of Matricaria camomillae. Extraction and quantitative determination of nicotine from the dried leaves of Nicotiniana tabaccum. Solid phase extraction and quantitative determination of xanthines from the dried leaves of Thea sinensis. Solid phase extraction with DPA-6S columns of curcuminoids from the pulverized roots of 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 (IOL) https://iol.unibo.it/, username and password are reserved only for Bologna University students.

Office hours

See the website of Federica Belluti

See the website of Maria Laura Bolognesi

See the website of Maria Laura Bolognesi

See the website of Alberto Leoni

See the website of Alberto Leoni