Chemistry Reference
In-Depth Information
O
NH
FIGURE 9.1
The basic beta-lactam ring structure.
N
S
O
N
O
OH
O
FIGURE 9.2
Chemical structure of penicillin G.
H
H
2
N
S
1
6
CH
3
2
5
7
N
CH
3
3
4
O
COOH
FIGURE 9.3
The structure of 6-aminopenicillanic acid, also known as 6-APA.
There were limits to penicillin G's clinical application, however, due to (1) the
presence of bacteria resistant to penicillin G, (2) the route of needing parenteral
administration, and (3) allergic susceptibility.
In 1957, the fundamental structure unit of penicillin G, 6-aminopenicillanic acid
(6-APA) (Figure 9.3), was announced. This discovery led to the production of new
semisynthetic penicillins. Chemical modifications were achieved on the 6β- amino,
the 6α, and the C3-carboxylic acid groups and these modifications significantly
improved the stability and potency. By introducing a moderately and sterically hin-
dered substitution group at the 6α position, this chemistry enhanced the resistance to
β-lactamase, an enzyme produced by bacteria to destroy penicillin. Currently, only
penicillin G and penicillin V are naturally occurring approved drugs, while the oth-
ers are all semisynthetic products.
9.2 STRUCTURE ELUCIDATION OF PENICILLIN
There are three chiral carbon centers in the 6-APA molecule. However, only the
isomer with the absolute configuration of 3S, 5R, and 6R possesses bioactivity. A
characteristic spectroscopic feature of β-lactams is featured in the infrared (IR)
spectrum (e.g., 6-APA is shown in
Figure 9.4). The v
max
(cm
-1
) of 1780 and 1660 are
diagnostic IR stretching bands of the β-lactam: representing C=O and amide C=O
Search WWH ::
Custom Search