Review of Organic Chemistry PDF

Review of Organic Chemistry in Preparation for Introduction to Medicinal Chemistry Mark J. Olsen Associate Professor of Pharmaceutical Science Phone: (623)572-3568 Email: [email protected] Office: Glendale Hall, Room 236-18  Chemica...

Review of Organic Chemistry in Preparation for Introduction to Medicinal Chemistry Mark J. Olsen Associate Professor of Pharmaceutical Science Phone: (623)572-3568 Email: [email protected] Office: Glendale Hall, Room 236-18  Chemical Properties Essential for Understanding Medicinal Agents 1. Acid/Base properties (pKa) and common acidic and basic structures. 2. Conformational analysis, aromaticity, resonance effects, and stereoisomerism. 3. Hydrophilicity and Lipophilicity. 4. Molecular interactions including hydrogen bonding, charge-charge, and hydrophobic/Van Der Waals interactions. Use of pKa in Drug Design  Basic Functional Groups ( 5 (5-6) - 6 2 Non-ionizable Functional Groups Spot the BASIC Amine! Conformational Analysis Regio-Isomers Aromaticity Resonance NO2 Worksheet O O O O O O N N N F F F F Aromaticity and Common Pharmaceutical Heterocycles N N N N Benzene Pyrazine Pyridine Quinoline N N N N O H H H Benzimidazole Benzofuran Indole Indoline N N N S O N N O O H H Thiophene Furan Pyrrole Imidazole Oxazole Isoxazole H N O O N N N H H H Pyran Piperadine Piperazine Morpholine Stereochemistry Is Extremely Important in Medicinal Chemistry Example of Different Biological Consequences of Different Stereochemistry or Regiochemistry  Assigning (R) and (S) Stereochemical Centers Identify chiral centers, usually carbons bearing 4 chemically distinct entities that can be arranged differently in 3D space. Rank chemically distinct entities using atomic number (and potentially isotope) to determine rankings. Place the lowest priority in the back, and use the “steering wheel” method to determine (S) for Sinister (Left) or (R) for Rectus (Right).  Practice Example H3 C H OH OH H3C H  The Least You Should Know: Medicinal chemistry is coming early in IS-1. Be prepared. Review your acidic and basic functional groups. On a given structure, is that Nitrogen basic? Is that H acidic? Stereochemistry is ALWAYS important. Can you assign R and S stereochemistry? Unlike in undergraduate organic chemistry, medicinal chemistry is all about HETEROCYCLES. What makes them similar? What makes them different?