Advanced Organic Chemistry (Bioorganic)

Learning Outcomes

Learning Outcomes

Having successfully completed this module you will be able to:

• Determine the biochemical origin of terpene and polyketide natural products. Understand the role of chemical mechanisms in the biosynthetic reactions leading to terpene and polyketide natural products
• Design the chemical synthesis of a short peptide, including the mechanisms of the proposed steps.
• Understand the chemical basis and mechanisms of the cellular pathways in glycolysis, amino acid biosynthesis and nucleotide biosynthesis.
• Explain the role of enzymes in natural product biosynthesis.
• Detail the structure of DNA and RNA, including the structure of the bases.
• Explain and detail the mechanism of the reactions used in solid-phase DNA synthesis.
• Detail the structure of amino acids, and how they assemble to form peptides and proteins.
• Understand the importance of natural products in the modern world.
• Discuss and describe the structure and synthesis of carbohydrates.

Nucleic Acids Chemistry

• Chemical structure and properties of nucleosides, nucleotides, nucleic acids.
• Structure and properties of DNA – A, B, and Z-DNA structures, Watson-Crick base pairing.
• The biological and biochemical mechanisms of DNA replication and transcription.
• Synthesis of nucleosides as drugs and for oligonucleotide synthesis, involving protecting group chemistry.
• Automated solid-phase DNA synthesis using phosphoramidite chemistry with emphasis on the reaction mechanisms of each step.
• The chemistry of nucleotide biosynthesis.

Enzymology and Protein Chemistry

• The structure of amino acids and the primary, secondary and tertiary structure of peptides and proteins.
• Mechanism of the serine proteases – the Asp-His-Ser catalytic triad and stabilisation of the tetrahedral oxyanion intermediate by hydrogen bonding.
• Molecular basis for the selectivity of the serine proteases – trypsin as compared to chymotrypsin.
• Mechanism of the methyltransferases
• Michaelis-Menten enzyme kinetics.
• The chemical reactions of glycolysis.

Carbohydrate Chemistry

An Introduction to Carbohydrates, their classification, structure and representation,

Mutarotation, anomeric effect, conformational equilibria, death-taxes-protecting groups,

Glycosyl donors/acceptors, polysaccharides and nucleosides.

Natural Product Biosynthesis

• Thioesters of co-enzyme A as acyl group carriers in biosynthesis.
• Chemical structure of terpenes (including monoterpenes, sesquiterpenes, diterpenes and polymers) and their derivation from isoprene units.
• The biosynthetic pathway to isoprenoids - Claisen-like, Aldol and decarboxylation mechanisms and the subsequent formation of isoprene equivalents illustrated by dimethyl allyl pyrophosphate (DMAPP).
• Terpene biosynthesis: The reaction steps fall into three classes: i) initiation: formation of the carbocation ii) propagation: rearrangement/reaction of the carbocation iii) termination: quenching of the carbocation. Formation of a wide variety of monoterpenes by quenching of the α-terpinyl cation.
• Biosynthesis of sequiterpenes, diterpenes and triterpenes.
• Fatty acid biosynthesis. Six key steps: i) thioester formation ii) C-C bond formation iii) ketone reduction iv) dehydration v) enoyl reduction vi) thioesterase.
• Polyketide and aliphatic polyketide biosynthesis. Aromatic Polyketide biosynthesis.
• Biosynthesis of 6-methylsalicylic acid, tetracylins. Modular polyketide synthases, erythromycin biosynthesis, engineering novel polyketide antibiotics.

Teaching and learning methods

Lectures, workshops

Resources & Reading list

Textbooks

J. McMurry and T. Begley. The Organic Chemistry of Biological Pathways. Roberts & Co.

Summative

This is how we’ll formally assess what you have learned in this module.

Referral

This is how we’ll assess you if you don’t meet the criteria to pass this module.

Repeat Information

Repeat type: Internal & External