Lecture 27

1. Lecture 27 • Hand in Lecture Problem 9 • Aldol Condensation • Drug Discovery • This week in lab: • 1st Synthetic Final Report Due • Next week in lab: • 2nd Synthetic Final Report Due & Lab Clean-Up

2. Aldol Condensation • Reaction highlights: • Run under basic conditions • Formation of a carbon nucleophile, an enolate • Enolate reacts with an electrophile, a carbonyl compound • A new C-C bond forms • First makes an b-hydroxy carbonyl compound (known as an Aldol • reaction) • Condenses (loss of H2O) to make • a,b-unsaturated carbonyl compounds • Example:

3. Aldol Condensation Example: Mechanism:

4. Mixed Aldol Condensation Mixed Aldol - use of two different carbonyl compounds; one will become the enolate (nuc), the other the electrophile Example: Mechanism:

5. Drugs Found in Nature: Natural Product Isolation Penicillin (antibiotic; isolated from mold) Taxol (anticancer drug; isolated from the bark of the Pacific yew tree)

6. Discovering Drug Candidates in a Chemist’s World Natural product isolation: - Herbs, berries, leaves, roots, marine life - Technique used: extraction & chromatography - Identify compounds via spectroscopic methods - Test compounds for biological activity 2. Synthesis -Produce compounds on a large scale -Synthesize derivatives of natural products (molecular modification) 3. Combinatorial chemistry -Generation of libraries of compounds that have similar structures -Test these derivatives for bio activity

7. Modern Drug Discovery • Prerequisites for an effective drug candidate: • Must react selectively with its target • Have minimal effect on host cell • Must have appropriate solubility to be transported to the • target cell • If taken orally, must be insensitive to stomach acid and be • resistant to enzymatic degredation before it reaches • target cell • Must be excreted or degraded to harmless compounds