full info on penicillin

1. Penicillin

2. • 1928: Alexander Fleming noticed that a mould
(penicillium notatum) produced a compound that
inhibits bacterial growth.
• 1940: Florey and Chain showed that an injection
of extract cured infections in mice and later in
humans.
• 1945: Fleming, Florey and Chain were awarded
a Nobel Prize for Medicine.

4. C
H
C
H
C
N C
H
C
C
CH3
CH3
S
NH
O
O
OH
C
CH2
O
C
CH
CH
CH
CH
C
H
Penicillin-G

5. Penicillin works by inhibiting an enzyme
involved in the building of bacterial cell walls.

6. The mould extract was broken down if
taken by mouth and effective only
against a limited range of bacteria.
In the 1950s it was shown that penicillin-G
could be broken down to give 6-amino
penicinillic acid from which a range of semi-
synthetic penicillins could be made.

7. C
H
C
H
C
N C
H
C
C
CH3
CH3
S
NH
O
O
OH
C
CH2
O
C
CH
CH
CH
CH
C
H
C
H
C
H
C
N C
H
C
C
CH3
CH3
S
N
H2
O
O
OH
6-APA

8. C
H
C
H
C
N C
H
C
C
CH3
CH3
S
N
H2
O
O
OH
C
O
Cl
R
C
H
C
H
C
N C
H
C
C
CH3
CH3
S
NH
O
O
OH
C
O
R

9. Unfortunately penicillins are fragile
C
H
C
H
N C
H
C
C
CH3
CH3
S
NH
O
OH
C
O
R
C
O
What is the bond angle here ?
What does it “want” to be ?
How can it get there ?

10. CH
C
H
NH C
H
C
C
CH3
CH3
S
NH
O
OH
C
O
R C
OH
O
Bacteria that have the enzyme β-lactamase
can hydrolyse the strained amide group.
These are resistant.
Suggest 2 ways of overcoming this resistance.
Why does this resistance spread?

11. 1) Make a
penicillin that
does not fit
into the
active site of
β-lactamase :
Methacillin
2) Inhibit β-
lactamase by
mixing the
active penicillin
with Clavulanic
acid
C
H2
C
H
C N
O
C
C
H
CH
C
O
H
O
CH2 OH
O
C
C
H
C
H
C
N
S
C
C
H
CH3
CH3
C
O
H
O
NH
C
C
CH
C
H
CH C O
O
O
C
C
O
H
H
H
H
H
H