Advanced Organic Chemistry (Bioorganic)

Fundamentals of Bio-organic Chemistry

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.

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.

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.
• .The chemistry of amino acid biosynthesis.

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.

Pre-requisites: CHEM2028 and CHEM2031