Chemical Biology What’s Chemical biology? Why should we learn? What should we learn? From chemistry point of view! What’s basic knowledge? What’s advanced knowledge?

Text book: March’s advanced organic chemistry, 6th edition Advanced organic chemistry A & B, Caery, Sundberg Name reactions and reagents in organic synthesis, Wiley, Mundy, Ellerd, Favaloro The organic chemistry of biological pathways, McMurry, Begley Protein-ligand interactions from molecular recognition to drug design, Wiley An introduction to Medicinal Chemistry, Third edition, oxford, Graham L. Patrick

Bond energy Acid & base Stereochemisty Reactivity Nucleophilic substitution Nucleophilic addition Caron-carbon bond formation Carbon-heteroatom bond formation Elimination Oxidation & Reduction Cyclization Cycloaddition

Vande Waals forces = 2-10 kcal/mol (9-40 kJ/mol) Covalent bond = 50-100 Kcal/mol (200-400 kJ/mol) Vande Waals forces = 2-10 kcal/mol (9-40 kJ/mol) electrostatic attractions, such as dipole/dipole/induced dipole/induced dipole (3) Hydrogen bonding = 6-8 kcal/mol (25-30 kJ/mol), dynamic form and break, 2x 10-12 S Exception = 50 kcal/mol FH----F bond Others = OH---O, NH---N bonds, 3-6 kcal/mol (12-25 kJ/mol)

(4) π- π interactions = Sandwich, T-shaped (I) and (II) (5) Hydrophobic interaction

stereochemistry (2) Methods of Resolution (1) Optical purity (2) Methods of Resolution (3) Cis-trans isomerism, configuration (4) Prochiral (5) Conformation (conformational energy), staggered/ eclipased (6) Strain, (small-angle strain) For example = 6-10 Kcal/mol

Acid and Base

Reactivity (1) keto-enol tautomerism = Table 2.1

Nucleophilic substitution R-X + Y R-Y + X SN2, SN2’ SN1 Neighboring-Group mechanism (p446) Nucleophile effect CN->I->OH->Br->CH3COO->Cl->NO3->>H2O Leaving group effect OTs>I>Br>OH2+>Cl>O+HR>OCOR>OAr

Nucleophilic addition

Caron-carbon bond formation 2+4 addition Aldol condition Grignard reagent or organometallic

Carbon-heteroatom bond formation Heterocyclic ring formation Amide or ester bond formation

Elimination beta-elimination

Oxidation & Reduction (1) R-OH / RCHO / RCOOH

Cyclization (1) Entropy effect

Cycloaddition 2+4 cycloaddition Heterocyclic ring formation

Basic Organic Reactions (W. McCrae) Functional Group Chemistry Acylation Alkylation Halogenation Oxidation reagents Reduction Reagents

Functional Group Chemistry Carbonyl Double bond Triple bond Conjugate system Nitrile Hydroxyl Ether Amino Halid OTs/OMs

Acylation (1) RCOCl>(RCO)2O>RCOOR’>RCOOH> RCONR2’ (2) Lewis acid as catalyst AlCl3>BF3>SnCl4>ZnCl2

Alkylation NO2>COR>SO2R>COOR>CN>Ph C-alkylation O-alkylation N-alkylation

Halogenation (1) –OH ----- -X

Oxidation reagents Ozonolysis Show other reagents

Reduction Reagents LiAlH4 NaBH4