1. 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?

7. 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

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

9. Vande Waals forces = 2-10 kcal/mol (9-40 kJ/mol)
Covalent bond = Kcal/mol ( 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 S
Exception = 50 kcal/mol FH----F bond
Others = OH---O, NH---N bonds, 3-6 kcal/mol (12-25 kJ/mol)

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

11. 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

12. Acid and Base

13. Reactivity
(1) keto-enol tautomerism = Table 2.1

14. 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

15. Nucleophilic addition

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

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

18. Elimination
beta-elimination

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

20. Cyclization
(1) Entropy effect

21. Cycloaddition
2+4 cycloaddition
Heterocyclic ring formation

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

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

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

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

26. Halogenation
(1) –OH X

27. Oxidation reagents
Ozonolysis
Show other reagents

28. Reduction Reagents
LiAlH4
NaBH4