Synthesis of Drugs

Code:

QF13004

Acronym:

SF

Keywords
Classification	Keyword
CNAEF	Chemistry

Instance: 2021/2022 - 1S

Active?	Yes
Responsible unit:	Organic and Pharmaceutical Chemistry Laboratory
Course/CS Responsible:	MSc in Pharmaceutical Chemistry

Cycles of Study/Courses

Acronym	No. of Students	Study Plan	Curricular Years	Credits UCN	Credits ECTS	Contact hours	Total Time
MQF	21	Official Curriculum	1	-	6	50	162

Teaching language

Suitable for English-speaking students

Objectives

 

The objective of this unit is to lead the students to understand the strategies and the methods applied to the synthesis of drugs and how this field is important in obtaining new drugs, such as novel or by molecular modification of a hit/lead compound. It is also intended that the students acquire a green chemistry point-of-view concerning the drug discovery and development process.

 

Learning outcomes and competences

 

At the end of the CU, students must have a broad and integrated understanding of the drug synthesis. The CU also aims to promote and develop critical thinking, teamwork and autonomy. At the end of the CU, students should be able to easily communicate their ideas, collaborate and work in team and to be able to solve problems using the scientific and investigational method.

 

Working method

Presencial

Program

 I. Theoretical

- The Organic Synthesis in Medicinal Chemistry
- Drug Synthesis : importance and examples .
- Drug Synthesis in the " discovery" and " planning " of new drugs .
- Libraries of compounds: definition, types and objectives .
- Methodologies for high throughput in drug discovery: combinatorial chemistry / HTS .
- Combinatorial Chemistry : solid phase on "split and mix" solution.
- Target oriented synthesis .
- Diversity -oriented synthesis.
- Retrosynthetic analysis: looking for a point in chemical space.
- Diversity of molecular skeletons : broad coverage of chemical space.
- Cross coupling reactions catalyzed by transition metals: examples .
- Olefin metathesis reactions: examples.
- Structure based design in drug discovery : examples
- Importance of the medicinal chemistry researcher in understanding the biological boundary of its activities: examples .
- Drug Synthesis: Importance of rules of Lipinski and other descriptors.
- Sustainable chemistry: importance of biocatalysis ; Examples of obtaining intermediates and drugs by the pharmaceutical industry .
- Sustainable chemistry : importance of " green " technologies ; synthesis assisted by microwave.
- Large scale synthesis of Drugs: the industrial reality.
- Campaigns and Lands in the pharmaceutical industry .
- Reactors and other equipment used in pharmaceutical industrial synthesis.
- Specifics of equipment , purity and control at different stages of the synthesis of drug intermediates and industrial level .
- Separation, purification and drying in industrial pharmaceutical synthesis.
- Working examples of the impact of the changeover operations on a small scale to large scale synthesis .
- How to improve reliability and efficiency: examples .
- Solvents to avoid and generally used in industrial synthesis .
- The importance of the phenomenon of polymorphism in drug synthesis . Examples .
- " Crystallization -induced asymmetric transformation ( CIAT ) " and " Crystallization -induced dynamic resolution ( CIDR ) " . Examples .
- Compliance with the regulations in drug synthesis: competent authorities (Infarmed, EMA and FDA) quality standards ICH .
- Retrosynthetic analysis, functional group interconversion : development and application to various organic molecules .
- Stereoselectivity and regioselectivity, examples.
- Examples of reactions used in the synthesis of pharmaceuticals and mechanisms involved :
Obtaining alkenes , alkynes , alkyl halides, alcohols, thiols, ethers, aldehydes and ketones, carboxylic acids and derivatives, aromatic compounds, amines and heterocycles (electrophilic addition, nucleophilic substitution, elimination , nucleophilic addition , nucleophilic acyl substitution, alpha – substitution, carbonyl condensation, reductive amination , rearrangements and pericyclic reactions).

II. Experimental

 

Partial syntheses reactions involving intermediate in the synthesis of many pharmaceuticals.
Synthesis of AAS assisted by microwave .

 

Mandatory literature

Stuart Warren, Paul Wyatt; Organic Synthesis: The Disconnection Approach, Wiley & Sons, 2008
Jie Jack Li, Douglas S. Johnson, Drago R. Sliskovic, Bruce D. Roth, 2004 John Wiley & Sons, Inc, New Jersey; Contemporary Drug Synthesis
James R. Hanson, W. Ed. H. Freeman Spektrum, 1995; An Introduction to Biotransformations in Organic Chemistry
Kappe C. Oliver; Practical microwave synthesis for organic chemists. ISBN: 978-3-527-32097-4
Pinto Madalena M. M. 340; Manual de trabalhos laboratoriais de química orgânica e farmacêutica. ISBN: 978-972-757-750-7
César Cornélio Andrei, Dalva Trevisan Ferreira, Milton Faccione, Terezinha de Jesus Faria, Ed. Manole, 2003.; Da Química Medicinal à Química Combinatória e Modelagem Molecular - um curso prático
John S. Carey, David Laffan, Colin Thomson and Mike T. Williams; Org. Biomol. Chem., 2006, 4, 2337–2347.
Manfred T. Reetz; J. Am. Chem. Soc. 2013, 135, 12480−12496J. Am. Chem. Soc. 2013, 135, 12480−12496
Neal G. Anderson; Organic Process Research & Development 2005, 9, 800-813
Ashley R. Longstreet, Suzanne M. Opalka1, Brian S. Campbell, B. Frank Gupton, and D. Tyler McQuade, Beilstein ; J. Org. Chem. 2013, 9, 2570–2578
Brittany L. Hayes; Aldricimica Acta, 2004, 37 (2), 66
Jeremy Everett, Mark Gardner, Frank Pullen, Graham F. Smith, Mike Snarey and Nick Terrett; DDT, 2001, 6(15).

Complementary Bibliography

Tieze Lutz F.; Domino reactions in organic synthesis. ISBN: 3-527-29060-5
Fieser Mary; Reagents for organic synthesis
Loupy André 340; Microwaves in organic synthesis. ISBN: 3-527-30514-9
Hudlicky Tomác5a1; The^way of synthesis. ISBN: 978-3-527-31444-7
Dc3b7rwald Florencio Zaragosa; Organic synthesis on solid phase: supports, linkers, reactions. ISBN: 3-527-30603-X
Wyatt Paul; Organic synthesis. ISBN: 978-0-471-92963-5
Johnson Douglas S. 340; The^art of drugs synthesis. ISBN: 978-0-471-75215-8

Teaching methods and learning activities

 

- Theoretical classes (3 hours/day): Presentations in “Power Point”; it is intended to transmit knowledge in an attractive and deductive manner. The literature sources indicated during class are also considered study material.

 

 

 

- The laboratorial tasks (6 hours/week) are performed in groups of 2 or 3 students, according to a chronogram. The logic of execution, its objectives and demonstration are previously explained in the theoretical and laboratorial classes.

 

- Some classes will be destined to the clarification of some matters and for solving some practical exercises in a way that stimulates the mind and taste for the subjects approached in theoretical classes.

 

- The lecturer responsible is available for students consultation on the times announced at the beginning of the semester or at a time previously arranged and agreed.

 

Evaluation Type

Evaluation with final exam

Assessment Components

designation	Weight (%)
Exame	100,00
Total:	100,00

Amount of time allocated to each course unit

designation	Time (hours)
Estudo autónomo	112,00
Frequência das aulas	30,00
Trabalho laboratorial	20,00
Total:	162,00

Eligibility for exams

 

a)Attendance to theoretical classes is not compulsory.

 

b)Students that do not achieve 9,5 in practical work distributed evaluation must perform a practical exam previously to the final exam in date according to the calendar.

 

c) Students that by law do not need to attend the practical classes, and do not have frequency in these classes must perform a practical exam previously to the final written exam in date according to the calendar.

 

Calculation formula of final grade

a) The assessment methods of the CU follow the stated in the "Evaluation Standards" of FFUP and consist of one component of assessment, which is performed by a final written examination, on subjects covered during the semester in theoretical e laboratorial lectures.
b) Students must obtain a minimum score on the final written test of 9.5 out of 20.

Special assessment (TE, DA, ...)

 

It is performed according to the evaluation standards FFUP. Students who, by law, are exempted from attending laboratory classes should perform laboratory exam and contact with the Responsible for the CU at the beginning of the semester.

Classification improvement

 

 

 

 

- Students must undertake the final written exam.