Anti-Infectives from Nature - Natural Products Chemistry: Sources, Separations, and Structures - page 91

100

50

0

4000 3000 2000 1500

Wave Number (cm -1 )

1000 500

FIGURE 9.4 IR spectrum of penicillin, 6-APA, clearly indicating the strong lactam C=O
stretch around 1780 cm -1 .

stretches, respectively. Further key structural features of penicillin compounds and
confirmation of their structures are supported by additional nuclear magnetic reso-
nance (NMR) and mass spectrometry (MS) spectral data.

9.3 ISOLATION OF PENICILLIN
The classical isolation method to obtain penicillin G from fermentation broth is
based on liquid-liquid extraction. The disadvantages of this method are (1) large
consumption of organic solvent and (2) low recovery rates. An alternate, more recent
method is now used to isolate penicillin G from the fermentation broth and this pro-
cess is known as aqueous two-phase extraction (ATPE).
The mechanism of ATPE is based on an adsorptive bubble separation technique
in which the surface-active compounds in water are adsorbed on the bubble surfaces
of an ascending gas stream and then collected in an organic phase as a layer placed
on top of the water column.
Typically, this process is carried out at room temperature and, first, upon comple-
tion of the fermentation, the broth is mixed with ammonium sulfate. This solution
is then adjusted to pH 6.8 with small amounts of HCl solution and NaOH solu-
tion, and then transferred to a floating ion cell. The penicillin G floats by bubbling
nitrogen gas at a flow rate of 40 ml/min from the bottom of the cell for 40 min, and
extracted into the polyethylene glycol phase on the surface of the sample solution.
Following the success of advances in fermentation technology and downstream
penicillin production, over the course of the next 40 years, many more β- lactam
antibiotics have been discovered and several are presented next.

9.4 CEPHALOSPORIN
In 1948, Giuseppe Brotzu discovered and isolated the first chemical compounds of
the cephalosporin group from Cephalosporium acremonium. Today, cephalosporin