Of streptothricin

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>. 

Further to complicate the structure of streptothricin, there is present a readily hydrolyzable urethan grouping involving an as-yet-undetermined... 

The biosynthesis of streptothricin F has been studied using H-labelled arginine substrates the results suggest that hydroxylation occurs with retention of configuration at C-4. ... 

For purposes of comparison, streptothricins F and D were applied to the chromatogram. When grown in the medium used in the experiments, the initial culture produces a mixture of streptothricins F and D... 

Streptothricin is a basic peptide, whose formula is C2oHg409Ng (581). It is antibiotic for diverse Gram-positive, Gram-negative, and acid-resistant bacteria (610), and is produced by certain strains of Streptomyces lavendulae (615). The isolation of streptothricin is as follows (455) charcoal adsorption, elution with dilute formic acid, precipitation by picric acid, and conversion of the picrate to hydrochloride, which is then purified by chromatography on either alumina or a mixture of Darco G 60 and paper pulp. The hydrochloride is converted to the crystalline helianthate which possesses a rotatory power Md = — 51.3° (c = 1.4in water). Other salts of streptothricin have been prepared, namely the reineckate (207), picrolonate, flavianate, dipicrate, and sulfate (555,581). According to... 

The chemical and antibiotic properties of streptolin are very similar to those of streptothricin and both contain isolysine (530). Streptolin differs in its rotatory power which, for the hydrochloride, is (a]i) = —22° (c = 1.8) and —25° (c = 2.9). It differs also by its adsorption behavior on Filtered, and also by its antibacterial activity, which is 6 times stronger than that of streptothricin in liquid media, but much weaker in an agar culture. This leads to the hypothesis that streptolin is more diffusible than streptothricin. 

The media used in the two types of t. sts an different and may, thereby, modify the action of the antibacterial substances. The influon c of alkalinity, salts, and phosphate concentration on the activity of streptothricin (73) can be cited as an example of the effect of composition of medium on activity. Several different media were used in the serial dilution methods. The kinds of media used in testing (when given in the original publications) are as follows Streak-plate method (104,115,145,146,160,162, 164,166,170). Serial dilution method in (a) beef extract, small inocula (96,102), and large inocula (158) (6) beef heart broth (119,122), small inocula (112,177), and large inocula (50,71,113) (c) beef heart dextrose (123), small inocula (132) (d) nutrient broth (107,158,165) (e) nutrient broth dextrose (57,118,158) (/) 1% tryptone broth, small inocula (134). 

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). 

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. 

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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