Streptomycin derivatives

S Additional information <1, 2> (<1> no activity with streptomycin derivatives that contain 3 -a-aldehyde groups [2] <1> no activity with N-amidinostreptamine, N -amidinostreptamine, N-amidinoinosamine, dTTP [1] <1,2> no activity with GTP, CTP, UTP [1,4]) [1, 4]... 

S Additional information <1> (<1> not streptomycin derivatives containing a 3 -a-aldehyde group [1] <1> not streptomycin 6-phosphate, UTP, GTP, CTP, streptomycin, dihydrostreptomycin, dihydrostreptomycin-3 -phosphate, dihydrostreptobiosamine [2]) [1, 2]... 

A great number of attempts have been made to improve the pharmacological and antibacterial properties of streptomycin. Most of the nthetic work dates from the years 1960—1968. Since then only a few new streptomycin derivatives have been described... 

From all the streptomycin derivatives, only the dihydrostreptomycin 6, which technically has been prepared by fermentation, is of importance. Bluensomycin plays no important role in therapy. 

Streptomycin derivatives Streptovitacin A degradation products Streptozocin (C8H15N3O7)... 

Tests of Function. Modified antibiotics were compared to the natural compounds in reversible binding to ribosomes and in inhibitory or other effects on ribosome function. In one case, the examination also included the in vivo effects of an antibiotic analog. In in vitro experiments, the interference by irreversible binding was prevented or minimized by performing the tests under conditions unfavorable for covalent reaction, e.g., low temperatures or suboptimal pH. Reversible binding studies were carried out with the clhoramphenicol and streptomycin derivatives and included the subunit localization of binding sites, estimation of the... 

Two new streptomycin analogues, ashimycins A and B, have been isolated from the fermentation broth of griseus these are streptomycin derivatives modified in the L-glucosamine unit, ashamycin A (1, part structure) carrying a glycosidically linked branched-chain sugar acid (the stereochemistry has not been established). ... 

Among the older aminoglycoside derivatives, kanamycin A and sisomicin were, at one time, a significant part of medical practice, but have now been largely replaced by the compounds Hsted in Table 1. Streptomycin is stiH used in a few restricted situations. 

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Amino sugars, such as o-glucosamine, have an OH group leplaced by an -NH2. The N-acetyl amide derived from o-glucosamine is the monosaccharide unit from which chitm, the hard crust that protects insects and shellfish, is made. Still otheramino sugars are found in antibiotics such as streptomycin and gentamicin. 

Streptose is the first branched-chain sugar to have been identified as a component of a biological compound produced by a microorganism. This dicarbonyl sugar is known only in its derivatives. The chemistry of streptose and streptomycin has been lucidly reviewed by Lemieux and Wolfrom.1 In this article, it was noted that streptose must be either 5-deoxy-3-C -formyl-L-ribose or 5-deoxy-3-C-formyl-L-lyxose. Since then, the presence of the latter configuration (XXXIV) has been definitely established by Wolfrom and DeWalt,66 who found that N-acetyltetrahydrostreptobi-... 

The other component parts of streptomycin, namely L-streptose and the aminosugar 2-deoxy-2-methylamino-L-glucose (A -methyl-L-glucosamine), are also ultimately derived from o-glucose. Gentamicin Ci contains two aminosugars, L-garosamine and D-purpurosamine. 

Following on the discovery of streptomycin and its streptamine-based relatives (Figure 1.2), a new generation of the aminoglycosides derived from 2-deoxy-streptamine (DOS) was not long in coming (Figure 1.3). For a variety of reasons, many of these compounds have not been employed as hnman therapeutics for... 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

Among the antimycobacterials often a differentiation is made between first-choice and second-choice agents. The first-choice agents include iso-niazid, rifampicin, ethambutol, pyrazinamide and streptomycin or as alternatives the other aminoglycosides amikacine or kanamycine. The second-choice agents include the quinolones ciprofloxacin and ofloxacin and also the rifamycin derivative rifabutin. 

The first suitable crystalline derivative of streptomycin that became available was streptomycin oxime sesquiselenate tetrahydrate.65 Streptomycin contains residues of the dibasic streptidine and of two... 

Mora and coworkers201 studied the in vivo interaction, in mice, of toxic levels of cationic macromolecules with the carboxyl and sulfate derivatives of polyglucose. Toxic levels of polymyxin, protamine, streptomycin, and neomycin could be counteracted, if the synthetic macroanions were injected five to ten minutes after administration of the proteins. Subcutaneous administration of the anionic polyglucoses prior to intra-peri toneal injection of toxic levels of basic proteins afforded protection to the mice, and also demonstrated that the animals could survive, even when the two injections were by different routes. 

Fluorescamine reacts with antibiotics which contain primary amine groups to produce highly fluorescent derivatives which may be detected in amounts as low as 38 pmoles/ml in solution [131]. Compounds such as Ampicillin, Kanamycin, Neomycin, Polymycin B and Streptomycin give positive results. The TLC method for biogenic amines (see Section... 

The conformations of streptomycin and streptomycylamine derivatives are calculated using the Hopfmger potential functions [226]. The conformations are opti-... 

Several compounds of this type, formally derived from aldoses by oxidation of the terminal CH2OH group to -CHO, have been prepared. Dialdoses arise as intermediates in structural studies, but they are also valuable starting materials for synthetic conversions, in particular for natural-product synthesis. A branched-chain dialdose, streptose (167), occurs as a component of the antibiotic streptomycin. The structure of streptose was elucidated after extensive investigations of its derivatives and transformation products.371 The 2,5-dimethoxytetrahydrofuran fulvanol (168), an analogue of apiose, has been isolated from the plant Hemerocallis fulva 12... 

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