Streptothricin antibiotics

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. 

In 2004, the gronp of Maruoka reported the direct asymmetric Mannich reaction of glycinate Schiff base 104 with a-imino ester 10a catalyzed by A-spiro-C -symmetric chiral quaternary ammoninm bromide 103 to provide the protected 3-aminoaspartate 105 in 88% yield (81 18 dr, 91% ee) [60]. The latter was afterwards converted into a precnrsor of the streptothricin antibiotics core structure (Scheme 5.43). 

C-Labelled D-glucose was incorporated into the 2-amino-2-deoxy-D-gulose residue present in racemomycin A, a streptothricin antibiotic. C N.m.r. measurements have been used to investigate the incorporation of D-[6- C]glucose into spectinomycin hydrate (390) by growing cultures of S. spectabilis. The... 

New streptothricin antibiotics, AN-201 I-III, elaborated by no.iirienis, have been characterized as N -acylated derivatives of... 

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. 

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. 

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. 

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). 

In contrast to the streptomycin-neomycin group of antibiotics, the members of the streptothricin group are not composed solely of carbohydrate moieties. In addition to the 2-amino-2-deoxy-D-guIose, the molecules contain one or more units of the unusual amino acid 3,6-diamino-hexanoic acid (jS-lysine) (10) together with a heterocyclic guanidine... 

Nitrogen metabolism plays a critical role in the biosynthesis of the streptothricin-type antibiotic nourseothricin in Streptomyces noursei [102]. Glutamine synthetase is repressed in this organism by a high concentration of ammonium ions. After the ammonium ion is depleted from the medium, derepression of the enzyme occurs. O-aminobenzoic (anthranilic) acid stimulates nourseothricin production and has a marked effect on regulation of enzymes responsible for nitrogen metabolism [102]. 

Some strains of Streptomyces are able to produce a series of antibiotics of similar activity they are designated streptothricines (StTs) (54JA566). Six substances with a similar behaviour were separated from different antibiotics of streptothridne group and were indexed as A-Fourth varying repeating units. The structure and properties of these antibiotics were extensively studied. 

Antibiotics of the streptothricine group are unstable in acid and especially in alkali. Their salts with mineral acids are insoluble in organic solvents, their IR spectra are identical, and the melting points of their salts are very similar (65KPS42). 

Streptothricins. A mixture of antibiotics of the nucleoside type first isolated in 1942 by Waksman and Woodruff from streptomycetes. S. were first considered to be a uniform substance and given the name S. F. The mixture was later found to consist of several, frequently occurring compounds that differ in the number of /3-lysine units in the side chain. 

C17H29N7O8 459.458 Streptothricin-type antibiotic. Isol. from Streptomyces griseodiromogenes and Streptomyces sp. No. 6241. Possesses weak antimicrobial activity and shows herbicidal props. Powder. 

Three years later the discovery of a second chemotherapeutic antibiotic, streptomycin, was reported by Schatz, Bugie and Waksman . Streptomycin was encountered in the course of a search for antibiotics among the acti-nomycetes. Members of this group of micro-organisms had been the subject of extensive study by Waksman and his colleagues. One of them had previously yielded the antibiotic streptothricin, which was too toxic to be clinically useful. 

The streptolidine lactam (1), a component of the streptothricin group of antibiotics, has been synthesized as outlined in Scheme 1 o-Glucose has been used as an optically active source material for the synthesis of a-multistriatin (2), a beetle hormone, which is summarized in Scheme 2, and of (- )-c/j-rose oxide (3), shown in Scheme 3. ... 

Streptothricins were shown to inhibit influenza in eggs and mice and the degree of activity appeared to be linearly related to the S-lyslne content.The activity of julimycin was attributed to an action of stimulating a host-defense mechanism not involving interferon." Paecilomycerol, a steroidal antibiotic, was shown to have antiviral activity without antibacterial or antifungal activity... 

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