The aim of this module is to introduce students to the fundamental principles that underpin modern organic chemistry.  Particular emphasis will be placed on relating each topic studied to examples of pharmacological significance.

Learning Outcomes:

By the end of this course students will have acquired an understanding of

·        Basic carbonyl chemistry

·        Acetals and sugar chemistry

·        Peptide synthesis, protecting groups and combinatorial chemistry

·        Aromaticity and the chemistry of five and six membered heterocycles

·        Chemistry of DNA and antivirals

·        Various aspects of stereochemist ry

·        Chemical bonding at enzymes and receptors

·        NMR

Introduction to Organic Reaction Mechanisms : Text (M. Hornbyand J. Peach; "Foundations

of Organic Chemistry," Oxford Chemistry Primers, Oxford Science Publications, 1993) 

1. Organic Reagents: Nucleophiles, Electrophiles, Radicals.
2. Resonance Structures
3. Curly Arrows
4. Electronegativity
5. Reaction Mechanisms: Substitution (S_N1, S_N2), Elimination (E1, E2)

Carbonyl Chemistry 1 ; Text : "Core Carbonyl Chemistry," J. Jones, Oxford Chemistry Primers, OUP, 1997, ISBN: 0198559593 See also CG&W, Chapter 6, Page 136)

1. The Carbonyl Group
2. Types of Carbonyls
3. Preparation of Carbonyls
4. Reactivity of the Carbonyl Group: Non Reversible Addition Reactions
5. Reversible Additions to the Carbonyl Group

Acetals  and Sugar Chemistry (Clayden, Greeves,Warren and Wothers) (CG&W), Chapters 6 and 49) 

1. Reversible Addition to the Carbonyl Group
2. Acetal Fomation
3. Intramolecular Acetal Formation
4. Sugars and Glycosides
5. Phase I and Phase II Drug Metabolism: The Chemistry of Glucuronidation

Carbonyl Chemistry  2 : Aldol Condensation  (CG&W, Chapter  27) 

1. Base cataysed Aldol
2. Acid Catalysed Aldol
3. Retro-aldol  in Biosynthetic Pathways
4. The Robinson Annulation- Steroid Synthesis

Amino Acid and Peptide Synthesis :  (CG&W, Chapter  25) 

1. Amides
2. Amide Structure
3. Peptides and Protein Structure
4. Protecting Groups
5. Selective Synthesis of a Dipeptide.

Aromaticity and Benzene Chemistry:  (CG&W, Chapters7 and 22) 

1. Aromaticity and the Hückel (4n +2π) Rule
2. Bonding in Benzene
3. Electrophilic Reactions of Benzene
4. Effects of Substituents on electrophilic Substitution
5. Nucleophilic Aromatic Substitution: Synthesis of Antibacterial Sulfones

Heterocyclic Chemistry 1:Pyridine Chemistry: (CG&W, Chapter 43) 

1. Pyridines
2. Naturally Occurring Pyridines and Important Pharmaceuticals
3. Bonding in Pyridine: Protonation of Pyridine and Water Solubility
4. Synthesis of Pyridines
5. Electrophilic Substitution
6. Nucleophilic Addition
7. Addition Elimination: Synthesis of Important  Pyridine  Containing Chemotherapeutic Drugs

Heterocyclic Chemistry   2:Pyrrole Chemistry : (CG&W, Chapter 43) 

1. Important  Pyrroles and Drugs Containing the Pyrrole Function
2. Bonding in Pyrrole
3. Electrophilic Substitution on Pyrrole
4. Deprotonation of Pyrrole
5. The Synthesis of Pyrroles

Heterocyclic Chemistry   3:Pyrimidines and Purines : (CG&W, Chapter 43) 

1. Nucleic Acids
2. Structure of DNA
3. Modified Nucleosides as Drugs
4. The Synthesis of AZT

 Static Stereochemistry (CGW&W chapt. 16) 

1. Stereoisomers
2. Chirality: enantiomers, chiral radiation (optical activity),chiral reagents (enzymes), asymmetric centres
3. Absolute configuration: R,S system, D,L, Fischer
4. Diastereoisomers
5. Resolution: chiral reagent, conversion intocovalent/non-covalent diastereoisomers, chiral         chromatography
6. Racemisation and epimerisation
7.  Prochirality: enantiotopic, diastereotopic

Dynamic Stereochemistry (CGW&W chapt. 18)  

1. Conformation and configuration
2.  Barriers to rotation around single bonds
3.  Linear alkanes: ethane, propane, butane
4. Substituted alkanes. Conformational Analysis of Acetylcholine
5. Cyclic alkanes: cyclo-propane/butane/pentane/hexane,substituted cyclohexanes

Chemical Bonding at Receptors and Enzymes (Nogrady, T., Medicinal chemistry - A biochemical approach , 2nd Edn Oxford U.P.,1990.) 

1. Hydrophobic Interactions
2. Hydrogen Bonding
3. Charge Transfer
4. Dipole Interactions
5. Ionic Bonds
6. Covalent Bonds

¹H NMR Spectroscopy (CGW&W chapt11) 

1. Chemical shift, field/frequency convention
2. The five regions: examples without ¹H-¹Hcoupling
3. ¹H-¹H coupling: examples
4. ¹HNMR of simple drugs

L15  Mass Spectrometry (Williams and Fleming, OCP Introduction to Organic Spectroscopy primer 43, chapt 6)

1. EI: fragmentation patterns
2.  High resolution: isotope peaks
3. Softer techniques: CI, FAB, ES
4. Importance of MS techniques in Pharmacology

Revision

This course will be taught by a series of lectures in Chemistry. Students will learn how to apply their knowledge by completing a series of related workshops.

1. Foundations of Organic Chemistry, M. Hornby and J. Peach (1995).  Oxford Chemistry Primers, Oxford Science Publications.
2. Organic Chemistry, J. Clayden, N. Greeves, S. Warren and P. Wothers (2001).  Oxford University Press.
3. Core Carbonyl Chemistry.  J. Jones (1997).  Oxford Chemistry Primers, Oxford Science Publications.
4. Medicinal chemistry – a biochemical approach.  T. Nogrady (1988) 2 ^ndedn.  Oxford University Press.Introduction to Organic Spectroscopy.  L.M. Harwood, T.D.W.Claridge (1997).  Oxford Chemistry Primers, Oxford Science Publications