Amides are widely found in both biological
systems and drug molecules. They are the most commonly formed functional group
in medicinal chemistry. Most amides are made from a carboxylic acid and an
amine by either conversion of the acid into an isolatable reactive intermediate
or by the use of an in situ coupling
agent. This course summarises the most commonly used reagents and methods for
the formation of amide bonds in the synthetic chemistry lab.
Alkylation of a heteroatom is a common transformation in synthetic chemistry. The heteroatom may be part of an amine, amide, sulfonamide, alcohol, phenol, carboxylic acid or heterocycle NH, amongst others. Treatment with a base and reaction with an alkylating agent such as an alkyl halide works in many cases, however more specialised reactions have been also been developed. In the alkylation of amines, reductive amination overcomes the issue of over-alkylation, whilst the Mitsunobu reaction can be used to alkylate acidic groups using an alcohol directly. This course summarises the most commonly used reagents and methods for heterocycle alkylation in the synthetic chemistry lab, paying particular attention to reductive amination and Mitsunobu reactions.
Protecting groups are used in synthetic chemistry to ensure a reaction occurs in a controlled manner and in as good a yield as possible. They may also be used to change the reactivity of a molecule to allow alternative chemistry to take place. This course summarises the functionalities most in need of protecting, commonly used reagents and methods to allow these transformations plus conditions to remove the groups when desired. A multistep synthesis of an approved drug is highlighted to show the usefulness of orthogonal protecting groups
6-Membered heteroaromatic rings are common in drug molecules. The structure of the ring can have a significant effect on the ADME properties of a compound. Pyridine is the most common in drugs but pyrimidine is also well represented. The other 6-membered rings are less common but are still seen. This course covers pyridine, pyrimidine, pyridazine, pyrazine and triazines. It describes some of the methods used to build the rings and touches on their reactivity towards electrophilic substitution, lithiation, nucleophilic aromatic substitution and palladium catalysed cross-coupling.
6,6-Bicyclic heteroaromatic rings are common scaffolds in drug discovery. This course covers quinoline, isoquinoline, quinoxaline, quinazoline, phthalazine, cinnoline, and the six naphthyridine isomers. It describes some of the methods used to build the rings and touches on their reactivity towards electrophilic substitution, nucleophilic aromatic substitution and palladium catalysed cross-coupling. Classical methods for forming bicycles wherein only one of the two rings contains one or two nitrogen atoms are described, whilst real-life drug discovery projects are used to exemplify the chemistry of the naphthyridines.
Stereochemistry is the study of chemistry in 3D and involves molecules which have the same molecular formula, but differ in their orientations in space. Chirality is one form of stereoisomerism involving molecules (enantiomers) in which their mirror images are not superimposable. Therefore, enantiomers have distinct structure and interact with biological systems in different ways. The course will develop awareness for different chirality forms and increase your knowledge of the important role that chirality has in the drug discovery process. Chiral purity and separation techniques will be discussed as well as the determination of the absolute stereochemistry.