37722 - Experimental Methodologies for the Preparation of Drugs (GR_B)

Learning outcomes

The course consist of theoretical lessons and pratical experiences in Lab. The course provide an overview of various tecniques of synthesis and extraction and of compounds of pharmaceutical interest. Moreover, major objectives are improvement of skill in the technical aspects of laboratory work (i.e. safe handling of chemicals, apparatus manipulation) and introduction to techniques and procedures important to the successful practice of experimental organic chemistry. Combinatorial and microwave-assisted synthesis will bealso discussed.

Course contents

Experimental methodologies for the preparation of drugs

Theoretical lessons

General instructions for safe working in organical chemical laboratories.
Apparatus and reaction procedures: glassware, apparatus with interchangeable ground glass joints suitable for general use in preparative organic chemistry: care and maintenance. Cooling and heating of reaction mixtures. Mechanical agitation.
Isolation and purification processes: Solids purification. Decolouration. Filtration techniques: filter funnels and membrane filters. Recrystallisation tecniques. Extraction theory. Solvent extraction. Countercurrent extraction: Craig apparatus. Solid phase extraction. Drying of solids and apparatus. Anhydrous reactions. Drying of liquids or of solutions of organic compounds in organic solvents: drying agents. Distillation. Rotary evaporator. Steam distillation. Fractional distillation at atmospheric and diminished pressure. Purification of common organic solvents. Silica gel column chromatography: flash chromatography.
Microwave-assisted synthesis of pharmaceutical compounds
Combinatorial chemistry in drug discovery. Solid phase synthesis.

Reactions mediated by transition metal catalysts.

Guidelines for keeping a Laboratory Record.

Laboratory practice
- Enantioselective enzymatic reduction of methylacetoacetate and purification by gravity-flow column chromatography.
-N-BOC protection of proline.
-Synthesis of tacrine.
-Synthesis of trans-9-(2-phenylethenyl)anthracene.
-Synthesis of nifedipine.
-Oxidation of isoborneol to camphor by potassium chromate.
-Reduction of camphor to isoborneol by sodium borohydride.
-Synthesis of p-nitroacetanilide and purification by flash chromatography.
-Synthesis of acetylsalicylic acid.
-Resolution of racemic 1-phenylethylamine by fractional crystallization.
-Extraction of trimyristine from Myristica Fragrans.
-Extraction of eugenol by steam distillation from Syzygium Aromaticum.
- Extraction of flavonoids and essential oil from dried flowers of Matricaria Camomilla.
- Extraction and quantitative determination of nicotine fron dried leaves of Nicotiana Tabaccum.
- Solid phase extraction and quantitative determination of xanthines from dried leaves of Thea Sinensis.

Readings/Bibliography

M. D'Ischia. La Chimica Organica in Laboratorio.(Tomo I e II).Piccin

D.L. Pavia, G.M. Lampman. Il Laboratorio di Chimica Organica. Sorbona

R. Morassi, G.P. Speroni. Tecniche Sperimentali del Laboratorio Chimico. Zanichelli

Vogel's. Chimica Organica Pratica. Casa Editrice Ambrosiana

V. Santagada, Caliendo G. Peptido e peptidomimetici. Piccin

V. Cavrini, V. Andrisano. Analisi farmaceutica. Metodi di riconoscimento e di separazione. Società editrice Esculapio

I.W.Wainer. Drug Stereochemistry, Analytical Methods and Pharmacology, M.Dekker, 1993

Assessment methods

A comprehensive final exam is given at the end of the semester and will include the preparation of a laboratory file.

Teaching tools

Videoprojector, PC, projector for transparencies, laboratory classes

Office hours

See the website of Marinella Roberti