Anti-Infectives from Nature - Natural Products Chemistry: Sources, Separations, and Structures - page 99

HISTORICAL NOTE

The avermectin story is a research collaboration between scientists in two
countries. In 1978, an actinomycete was isolated at The Kitasato Institute,
Tokyo, Japan from a soil sample collected at Kawana, Japan, and the iso-
lated actinomycete was sent to Merck Sharp and Dohme for testing. Early
tests indicated activity against Nematospiroides dubis in mice without tox-
icity. Subsequently, the anthelmintic activity was isolated and identified as
a family of closely related compounds in 1978.

occurring compounds are generated as fermentation products by Streptomyces aver-
mitilis , a soil actinomycete. Eight different avermectins were isolated as four pairs
of homologous compounds, with a major (a-component) and minor (b-component)
component, usually in ratios of 80:20 to 90:10.

9.15 TETRACYCLINES
Tetracycline compounds form another group of broad spectrum antibiotics whose
general usefulness has been reduced with the onset of bacterial resistance. They are
defined as a subclass of polyketides having an octahydrotetracene-2-carboxamide
skeleton (Figure 9.18). Tetracyclines are generally used in the treatment of infections
of the urinary tract and the intestines, and are used in the treatment of infections
caused by chlamydia, especially in patients allergic to β-lactams and macrolides.
However, their use for these indications has decreased due to widespread develop-
ment of drug resistance to these compounds. Their most common current use is in
the treatment of moderately severe acne and rosacea. In addition, they may be used
to treat Legionnaires' disease. They also are used in veterinary medicine, particu-
larly on swine.

OH O OH OH O

NH 2

OH

N

FIGURE 9.18 The tetracycline ring structure exhibiting the four contiguous rings.