Monash University Handbook 2010 Undergraduate - Unit

Synopsis

This unit describes the chemical technologies used in the drug discovery and development process to illustrate advanced chemistry. The unit will build on the previous units of the Bachelor of Pharmaceutical Science. Assignments will be carried out in small teams and will help the students learn how teams work together. Topics include:

• Combinatorial Chemistry and Diversity-Oriented Synthesis: to introduce students to the fundamental principles of combinatorial and diversity-oriented synthesis, as applied to lead discovery and optimisation,
• Ionic Liquids: to introduce the properties and use of alternative solvents such as ionic liquids and supercritical fluids in the synthesis of drugs,
• Synchrotrons for medicinal chemists: to introduce students to synchrotron science and explore its uses and possible uses in chemistry and drug design,
• Click Chemistry and Fragment-based drug discovery: have a broad understanding of the various fragment-based approaches to drug discovery,
• Microreactors/ Microfluidics: to introduce the use of microreactors and microfluidics in synthesis and pharmaceutical preparation,
• Process chemistry: to introduce aspects of process development including reaction optimisation by minimizing handling, optimising transformations and reducing impurities. Large scale purification methods, reaction pathway, solvent and reagent sources.

Objectives

After completion of this unit, students will understand the important modern chemical technologies in the pharmaceutical sciences, and be expected to be able to discuss the following topics:

1. Combinatorial Chemistry and Diversity-Oriented Synthesis:
• Comprehend the basic principles and defining features of combinatorial chemistry and diversity-oriented synthesis;
• Appreciate the utility (and limitations) of combinatorial chemistry and diversity-oriented synthesis in identifying biologically active lead compounds;
• Describe several methods for identifying biologically active compounds within a combinatorial library;
• Contrast the methodology and equipment used in "mix-and-split" versus parallel syntheses, and solid-phase versus solution-phase syntheses;
• Comprehend the chemistry involved in solid-phase peptide synthesis and the synthesis of a number of heterocyclic compound libraries.
2. Ionic Liquids:
• Have a knowledge of alternative solvents of use in synthetic chemistry applications, specifically as applied to synthesis of drugs and drug-like molecules - advantages and disadvantages;
• Be able to describe the types of ionic liquids, as well as their synthesis and properties;
• Have a knowledge of the use of ionic liquids in synthesis;
• Be able to describe the use of supercritical CO2 in synthesis, with specific reference to controlling stereoselectivity in drug synthesis;
• Be able to describe the use of high temperature water in synthesis.
3. Synchrotrons for medicinal chemists:
• To explore how synchrotrons work and understand the properties of synchrotron light;
• To explore the advantages of using synchrotron sources when compared with laboratory sources;
• To develop an understanding of the great range of synchrotron beamlines and their primary uses;
• To explore in more detail the beamlines that are likely to be of use to medicinal chemists;
• To develop a knowledge of synchrotron applications in drug design, drug synthesis, drug analysis and drug interaction;
• Describe and understand how synchrotrons operate, have a knowledge of all the beamlines on the Australian synchrotron and understand the synchrotron advantages;
• Understand in greater detail the beamlines of importance to medicinal chemists;
• Demonstrate a knowledge of the applications of synchrotrons that are relevant to chemists;
4. Click Chemistry and Fragment binding:
• Understand the process of identifying and linking low affinity molecular fragments to product higher affinity ligands for a target biomolecule;
• Have a detailed knowledge of the principles and key reactions involved in dynamic combinatorial chemistry and click chemistry;
• Appreciate the scope of reactions and methods used in linking fragments in situ
• Have a knowledge of the use of x-ray crystallography and mass spectrometry in fragment-based approaches to drug discovery;
• Be familiar with successful examples where a fragment based approach has resulted in high affinity ligands for protein targets.
5. Microreactors/Microfluidics:
• To understand the benefits and problems associated with the use of microreactor and microfluidic methods in the synthesis of pharmaceutically important substances.
6. Process Chemistry:
• To recognise the major factors which drive process chemistry;
• To recognise the challenges involved in transferring discovery processes into large scale process synthesis;
• Appreciate the roles that route, reagent, solvent selection, safety and waste generation play on chemical processing;
• Be able to apply knowledge of the above to transform an expedient synthesis into an optimal synthesis.

Assessment

Final exam (2.5 hour): 75%; written assignments: 25%.

Chief examiner(s)

Dr Jamie Simpson

Contact hours

36 1 hour lectures and whole class tutorials as requested

Prerequisites

PSC2011 Pharmaceutical biochemistry
PSC2021 Analytical methods
PSC2121 Synthetic chemistry I
PSC2141 Computational chemistry I
PSC2062 Pharmacology
PSC2082 Introduction to spectroscopy
PSC2092 Molecular cell biology
PSC2122 Synthetic chemistry II

Additional information on this unit is available from the faculty at:

http://www.monash.edu.au/muso/