Having completed this module the students will have: Advanced knowledge of the synthesis and reactivity of wide-range of aromatic heterocycles and cyclic structures, especially those with relevance to Pharmaceutical drugs; the mechanisms involved in these syntheses will be studied in detail; studies of natural products and analogues, will be undertaken to demonstrate this very important source of pharmaceutical drugs. Phosphorus and sulfur chemistry, as well as palladium catalysed coupling reactions (Heck, Still, Suzuki, etc.) in drug synthesis; Design methods for multistep routes to important pharmaceuticals and privileged structures, emphasising cyclic compounds; Spectroscopic and other methods of structural elucidation to a level allowing identification of unknown drug and drug intermediate substances, including treating a product of a synthesis as “unknown” until the structure is proven; Spectroscopic methods of establishing purity of products of such syntheses.
Heterocyclic Chemistry
Describe the synthesis and reactivity of aromatic heterocyclic ring systems and their applications in drug synthesis, through case studies. Non-aromatic hetero-cyclisation reactions – explanation of Baldwin’s Rules, etc.
Natural Product Chemistry
Synthesis and Biosynthesis of natural products and their use as bioactive molecules
Phosphorus, Sulfur and Palladium reagents in Drug Synthesis
Phosphorus reagents (e.g. ylids, Mitsunobu reaction, Arbuzov reaction); sulfur reagents (e.g. ylids, Swern oxidation, dithianes); Palladium catalysed cross-couplings (Heck, Stille, Suzuki reactions) and their mechanisms.
Multistep Synthesis
Route development to important pharmaceuticals and privileged structures. Target molecule fragmentation back to simple starting materials. Control of cross-condensation reactions. Drawing and discussion of mechanisms of each step.
Structural Elucidation
1H-NMR, including HH-CoSy, examples of diamagnetic anisotropy, and a detailed description of hydrogens on heteroatoms (effects of solvent, impurity, concentration); 13C-NMR, including proton-coupled i.e. 13C and proton-decoupled i.e. 13C{1H}, and use of DEPT-90/-135 spectra. Heteronuclear 2D techniques: HSQC & HMBC; other NMR nuclei important in drugs. Information obtainable from molecular formula. Use of other data (solubility & other physical properties, “wet” tests).In-class work will strike a balance between “structures from spectra” (identification of a compound from spectra) and “spectra from structure” (advance prediction of spectra for a structure, including predication of alternative products/isomers where relevant, especially for relevant laboratories).In-class work and continuous assessment to include identification of an unknown drug or drug intermediate substance, given spectroscopic (NMR, IR, etc.) and other data (molecular formula, solubility & other physical properties, results of “wet” tests), with an emphasis of integration of new techniques with those previously covered, and on appropriate deductive logic to narrow a search down to a few likely suspects, and then to eliminate suspects to achieve identification.
| Module Content & Assessment | |
|---|---|
| Assessment Breakdown | % |
| Other Assessment(s) | 30 |
| Formal Examination | 70 |