Streptothricines

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Daniels Structure of the Aminosugar derived from Streptothricin and Streptolin B. J. Amer. chem. Soc. 78, 4817 (1956). 

Colimycin, Colistin(not to be confused with Polymixin), Dextromycin,Flavomycin,Fradiomycin, Framycetin, Mycerin, Mycifradin, Neomix, Sofra-mycin, Streptothricin BI, BII. 

The resulting substances were named streptothricin Bl289f mycerin290 and colimycin291, but have since been shown to be identical to the neomycin complex. 

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

A group of soil actinomycete Streptomyces nojiriertsis have been identified as producing derivatives of streptothricin antibiotics of the general structure (654) which incorporates a hexahydro imidazo[4,5-c]pyridine system into the molecule <87JAN1140>. The total synthesis of streptothricin F has been reported <82TL296i>. 

Cyanogen bromide ring closure of (417) was used to prepare streptolidine lactam (418), a guanidine-containing amino acid lactam moiety of the streptothricin antibiotic group (77BCJ2375), that moiety being a 4,5,6,7-tetrahydroimidazo[4,5-c]pyridine. 

The actinomycetes (order Actinomycetales) are nonmotile organisms that may be considered as intermediate forms between bacteria and molds. They occur abundantly in soils, composts, river and lake bottoms, in dust particles, and upon plant surfaces. The order is divided into three families comprising a number of genera. These genera are represented in nature by many thousands of species, of which several hundred have been scientifically characterized. Recent interest in the antibiotics elaborated by the actinomycetes first centered on the substance streptothricin, isolated from Streptomyces lavendulae (formerly named Actinomyces lavendulae). When this antibiotic was found to exhibit dangerous delayed toxicity effects, attention was turned to streptomycin, which had been isolated from the culture medium of a related organism. 

The separation of aminodeoxy sugars from neutral and acidic sugars may be readily achieved using an acetate buffer at pH 5 (the iV-acetyl derivatives of D-glucosamine and n-galactosamine have characteristic Mg values in borate buffer at pH 10). M. C. Foster and Ashton have found zone electrophoresis to be useful in the separation of streptomycin components. They observed the following mobilities X 10 ) streptomycin, 22.5 mannosidostreptomycin, 19.5 streptothricin, 24.0 streptidine, 24.9 and streptamine, 6.3. 

Structures (Figure 1.9) have been proposed for etamycin, echinomycin, albomycin, ilamycin, telomycin, viomycin, valinomycin and for some members of the streptothricins, the actinomycins and the vernamycins. Syntheses have only been achieved for valinomycin and some members of the actinomycins. 

Waksman and his collaborators grew a batch of a soil microorganism called Actinomyces griseus and isolated their first antibiotic from the brew in 1940. They called it actinomycin, after the species of microorganism from which it was isolated. In 1942 they isolated streptothricin. Like actinomycin, it was too toxic to use in humans, but unlike actinomycin, it destroyed the tubercle bacillus. Encouraged by these discoveries, Waksman continued to test, or screen, other soil microbes for their ability to produce antibiotics with activity against the bacteria that caused tuberculosis (now known as Mycobacterium tuberculosis). 

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