Anti-Infectives from Nature - Natural Products Chemistry: Sources, Separations, and Structures - page 95

Both nocardicins and monobactams possess similar mechanisms of action as
other β-lactam antibiotics and act as imitators of penicillin-binding proteins, PBPs,
in bacteria cell wall formation. Although no valuable antibiotic based on modifying
nocardicin A was found, its simple structure without a bicyclic ring core structure
indicated that a bicyclic core structure found in the more traditional β- lactam anti-
biotics may not be necessary. The monocyclic nucleus only has one four-membered
ring, which has less ring strain in comparison to penicillin. A less rigid structure
leads to the lower activity of the β-lactam ring. As a result, norcardicin A possesses
only moderate activity in vitro against some gram-negative bacteria. It is a narrow
spectrum antibiotic.

9.9 ISOLATION

Nocardicin A can be obtained directly from the crude fermentation broth as an anti-
biotic mixture using the following scheme and then recrystallized from aqueous eth-
anol. In this example, a macroporous resin, Diaion HP20 was used in a similar way
to XAD resins, which absorb the crude antibiotic mixtures onto the resin matrix.

nocardia uniformis Broth Filtrate, pH 4

Sorb on Diaion HP20 resin and elute with MeOH-H2O, 3:7.

Concentrate in vacuo and acidify to pH 2.5 (HCl).
Crude antibiotic mixture

Chromatograph on Diaion HP20 resin
Adj to pH 7 (NaOH)
1. Elute with 3% NaCl
Nocardicin A

2. Continue elute with MeOH-H2O, 3:7, followed by concentration and
acidification to pH 2.3 (HCl)
Nocardicin B

9.10 CARBAPENEM

The simplest naturally occurring carbapenem antibiotic has the core structure shown
in Figure 9.12. Other carbapenem antibiotics are based on this core, with substituted
groups on C2 and C6. The first carbapenem antibiotic, thienamycin (Figure 9.13), was
also first discovered in 1976, isolated from the fermentation broth of Streptomyces