O

HO

HO

N

HH

CH3

O

H3CO

HO

N

HH

CH3

O

H3CCO

H3CCO

N

HH

CH3

O

O

morphine codeine heroin

Ibuprofen

OH

O

H3C H

OH

O

H CH3

R formnon-activeside effects

S formactive

anti-inflammatory

R.B. Woodward (1917-1979)

•1965 Nobel Prize in Chemistry•“outstanding achievements in the art of organic synthesis

•Also made VERY important observations in the development of the Woodward-Hoffman rules of ring closure•1st step in the application of quantum mechanics to organic molecules•1981 Nobel Prize in Chemistry (Roald Hoffmann)

•1st modern synthetic organic chemist•Probably greatest organic chemist

R.B. Woodward (Early Career)

Ferrocene

Fe

Penicillin V

N

S

O

NH

H

H

COOH

CH3

CH3

PhOH2C

O

Tetracycline

OH O OH O

CONH2

OH

N(CH3)2H

H3C OHH

OH

R.B. Woodward (Later Career)

Quininewith von E. Doering, 1944

N

OCH3

NHO

H

HO

CH3 H

CH3

H H

Cholesterol1951

Reserpine1956

NH

NH3CO

H

H

H

OCH3H3COOC

O

O OCH3

OCH3

OCH3

Cephalosporin C1966

NS

N

O

O

CH3O

NH3

OOC

OH

HOOC

R.B. Woodward

Vitamin B12with Eschenmoser, 1972

N

N N

N

CH3

CH3

Co

H3CH3C

CH3

CH2CH2CONH2

CH3H

H

CH3 H

CH3

H

CONH2

H2NOC

H2NOC

H2NOC

NH

O

OP

O

O

O

O

OH

N

N CH3

CH3

HO

CONH2

H

H3C

K.C. Nicolaou

•Penn (1977-1989)•Scripps Research Institute and UC-San Diego (1989-present)•Modern day R.B. Woodward

K.C. NicolaouTaxol

OH

O

HO

AcO

AcOH

OBz

O

O

NH

Ph

O OPh

OH

11 stereocenters => 211 = 2048 stereoisomers2 rings & 1 bicyclic ring

• Isolated in 1967 from bark of Pacific yew tree• Lung, ovarian, breast, head and neck cancer

K.C. NicolaouBrevotoxin B

23 stereocenters => 223 = 8,400,000 stereoisomers11 trans-fused rings83 steps, 12 years91% yield for each step but 0.043% total yield

O

O

O

O

O

O

O

O

MeH Me H

H

Me Me H

MeH H H

HH H

OO

O O

H

H

H

HO

Me

H

H

HO

Me

• Neurotoxin that binds to voltage-gated sodium channels in nerve cells

• Naturally found in Karenia brevis which are marine organisms typically found in fish

K.C. NicolaouMaitotoxin

94 stereocenters => 294 = 1.98 x 1028 stereoisomers31 trans-fused rings

• Neurotoxin that binds to calcium channels• Naturally produced by Gambierdiscus

toxicus which are marine organisms typically found in fish

Atomic Orbitals

n l Orbital Name

1 0 1s

2 0 2s

2 1 2p

3 0 3s

3 1 3p

3 2 3d

n l ml Orbital Name

1 0 0 1s

2 0 0 2s

2 1

-1

2p0

+1

3 0 0 3s

3 1

-1

3p0

+1

3 2

-2

3d

-1

0

1

2

Linus Pauling (1901-1994)

• “The Nature of the Chemical Bond”• Protein Structure• Antibody Structure and Process• Molecular cause of Sickle-cell anemia• Electronegativity• Resonance• Vitamin C and the Common Cold

• Probably greatest chemist of the 20th century

• Only person too win 2 unshared Nobel Prizes and only person to win 2 unrelated Nobel Prizes• 1954 – Chemistry• 1962 - Peace

The Periodic Table and Electronegativity

Common Bonding Situations

Hydrogen 1 bond O HH

Carbon 4 bonds (neutral and 8 electrons)

C C

H

H

H

H

H

H4 single bonds

C C

H

H

H

Hdouble bond

C CH H

triple bond

Reactive Carbon Species

CH

H

H

+

carbocation

CH

H

Hradical

CH

H

H

_

carbanion

Nitrogen 3 bonds and one unshared pair of electrons

C N

H

H

H H

H C N

H

H

H

C NH

Other relatively stable species

NH

H

H

H

+

4 bonds + charge

NH

H2 bonds2 pairs

- charge

_

Oxygen 2 bonds and 2 unshared electron pairs

C O

H

H

H

H C O

H

H

Other relatively stable species

OH

H

H+

3 bonds1 pair+charge

H O

_

1 bond3 pairs

- charge

hydronium ion

Halogens 1 bond and 3 unshared electron pairs

C BrH

H

H

also 4 unshared pairs and negative charge

Cl_

Table 2-6a, p. 51

Table 2-6b, p. 51

These are sigma () MOs: symmetrical about the internuclear axis

OO

C

O

C

O

O

C

O

Energy