Curriculum Information

Topics covering will include, but are not limited to:-

1) Chirality and Conformational Analysis

Chirality: Revision of chirality in carbon systems containing one chiral centre and extension to systems containing multiple chiral centres. Chirality in systems lacking a stereogenic carbon atom. Point chirality: tertiary amines, sulfoxides,  phosphines. Axial chirality: allenes and hindered biphenyls. Assignment of stereochemistry in  these systems. Helical structures. Prochirality and facial chirality Si,  Re.

The importance of chirality and conformation and its role and importance in the pharmaceutical industry

Conformational Analysis: Ethane and butane. Newman projections and energy -  plots. Terms used include staggered, eclipsed, gauche, anti-conformations. Strain in acyclic  molecules: consequences on conformations. 6-Membered rings (how to draw). Axial and equatorial hydrogens. Chair, half chair, twist  chair, boat. 6-Rings. A-values - gauche and syn-pentane interactions (1,3-diaxial);  experimental evidence.

Ring size strain for cyclopropane, cyclobutane, cyclopentane. Medium rings and transannular  strain. Stabilising electronic effects upon conformation.

Sugars and the anomeric effect. Esters and amides;  peptide bond; phosphodiesters in DNA.

2) Introduction to Reactivity

Basics of reactive intermediates. Inductive and resonance effects on stability. Rate determining steps and reaction profiles. Stereoselectivity and stereospecificity definitions  Kinetic and thermodynamic  control. Basicity and nucleophilicity: hard and soft; pKa vs. nucleophilicity. The alpha effect.

Fundamentals of carbonyl reactions. Additions and additions/eliminations. General trends in reactivity. Sterics and  electronics. Kinetics of hydrolysis and esters and amides: Rates and mechanistic interpretation.

Diastereoselective Reactions. for carbonyl additions. Development of  models for understanding experimental results: Felkin-Anh model.

Acid and Base Catalysis: Mechanisms and catalysis – looking at  ester hydrolysis and inferring mechanism. Specific acid catalysis, General acid catalysis. Specific base catalysis, General base catalysis. Enzymatic catalysis – chymotrypsin. Termolecular base amide hydrolysis

Heterocyclic Systems and Reactivity: Identification of basic heterocyclic systems and aromaticity. Substituent effects on physical properties such as acidity and solubility.

Linear free energy Relationships and Structure Reactivity Relationships: their importance in the pharmaceutical industry

QSAR; Mechanistic investigations. Substituent effects on acidity and pKa.

3) Biological Macromolecules: Their Cellular Function and as Targets in Medicinal and Pharmaceutical Science

Carbohydrates: Cellular energy and glucose; the structure of D-glucose, anomers and the anomeric effect; the  structures and functions of monosaccharides; the glycosidic bond; oligosaccharides – structures  and functions of disaccharides and polysaccharides; biosynthesis of oligosaccharides.

Nucleic Acids: Introduction to nucleic acids and their structure. Structure of bases.  Base paring. 3D structure. Structure of DNA and RNA.

Lipids: Be familiar with the physical and chemical properties and biological function of each of the families of lipids. Name the common lipids. Know the structure and functions of cell membrane. Know the method of synthesizing glycerides and the reactions of glycerides: esterification, hydrolysis, saponification, and hydrogenation. Be familiar with the structure of steroid hormones. Understand the role of the lipoproteins in triglyceride and cholesterol transport in the body. Appreciate the roles of HDL, LDL, and cholesterol.

Proteins, Enzymes &  Receptors: Protein structure; Chirality; Enzyme catalysis, transition state  theory, Michaelis-Menten kinetics, selected examples of enzyme catalytic mechanisms; use of  enzymes for biocatalysis, resolution of enantiomers. Structure of receptors and binding of small molecule ligands via intermolecular interactions.