Lecture Notes: Frontline Chemistry and Natural Product Synthesis

Introduction

• Speaker: Third year DPhil student in Professor Darren Dixon's research group
• Focus: Connection between organic molecules, organisms, and medicine effectiveness

Background

• Origin: Grew up in North Essex, studied at University College, Oxford
• Specialization: Passion for organic chemistry
• Current Program: Synthesis for Biology and Medicine DPhil

Key Concepts

Skeletal Formulae

• Simplified representation of molecules
• Carbon-carbon bonds shown as lines; hydrogens are implicit

Total Synthesis

• Definition: Construction of complex molecules from simple precursors
• Process involves many chemical reactions (steps)

Natural Products

• Produced by living organisms
• Primary vs. Secondary Metabolites
  • Primary: Present in many organisms (amino acids, sugars)
  • Secondary: Specialized compounds (pheromones, antibiotics)

Historical Examples

Penicillins

• First antibiotics, discovered in early 20th century
• Profound impact on modern medicine

Artemisinin

• Anti-malarial treatment from sweet wormwood
• Discovered by Yu Yu (Nobel Prize in 2015)

Challenges in Drug Discovery

• Increasing cost and complexity of drug development
• Factors:
  • Screening compounds
  • Effectiveness and safety trials
  • Regulatory approval

Current Trends

• High number of carbon-carbon double bonds in drugs
• Comparison: Natural products are more three-dimensional

Isolation and Purification of Natural Products

• Techniques: Chromatography, spectroscopic analysis
• Examples: Pyrethrin-1, Plurimutalin, Artemisinin

Importance of Chemical Synthesis

Case Study: Taxol

• Anti-cancer drug from the Pacific yew tree
• Synthesis critical due to endangered source

Work in the Dixon Group

• Focus on developing new chemistry through synthesis
• Example Projects:
  • Manzamine A: Marine sponge, insecticidal and antibacterial
  • Himalensin A: Nepalese shrub, new chemical reactions
  • Nakadomarin A: Collaboration with MIT

Optical Isomerism and Chirality

• Definition: Molecules that cannot be superimposed on mirror images
• Importance in chemical synthesis and drug development

Retrosynthesis

• Concept of working backwards from a target molecule
• Enables identification of simpler precursor molecules

Case Study: Medangamine E

• Project involving retrosynthesis and enantioselective chemistry
• Successful synthesis after 30 steps

Current and Future Work

• Dapholdendron B: New natural product with potential biological activity
• Focus on efficient and green synthesis methods

Conclusion

• Nature's chemistry as an inspiration for solving medical issues
• Natural product synthesis is key to advancing drug discovery

Topics Covered

• Skeletal formulae, optical isomers, chirality, enantioselectivity, purification, and analytical methods

Acknowledgements

• Industrial sponsors, Magdalen College, Supervisor Darren Dixon, Research Group members

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