Aminoglycoside derivatives

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. 

Structure-Activity Relationships Among Aminoglycoside Derivatives... 

Estimated worldwide sales are given in Table 1 for the aminoglycoside derivatives most commonly used in medicine. Although amikacin has somewhat higher sales, gentamicin is by far the most widely used in terms of number of courses of treatment. 

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... 

The anthracyclines are aminoglycosidic derivatives of tetracyclic compounds that contain an anthraquinone chromophore. Originally, dauno-mycin and adriamycin, its hydroxy analogue, were isolated from cultures of Streptomyces peucetiusd The main target of these drugs appears to be DNA, most likely by formation of an intercalation complex. The drugs also affect topoisomerase II, an enzyme which interacts with the DNA that has been modified by intercalation. ... 

To test these findings, new aminoglycoside derivatives were synthesized in a series bearing either one or both of these recogiution motifs for RNA interaction... 

Figure 6-21. Aminoglycosides derived from streptidine-streptomycin (SM).

The number of aminoglycoside derivatives reported over the years is verylaige. Much of the work has been summarized in reviews (120,122—125). Only the stmctural subclasses and representative derivatives are discussed here. Some of the stmctures are given in Table 2. 

In the case of aminoglycosides, we have applied the OPopS technology on a unique aminoglycoside core, prepared from known antibiotic tobramycin, to produce variety of aminoglycoside derivatives. Among them, confound OP-382 was identified as a novel, promising lead that is active against a variety of bacteria strains. Further optimization is now underway in our laboratory. 

A review on semi-synthetic antibiotics invulnerable to enzymes of resistant bacteria includes references to aminoglycoside derivative. ... 

A. Lapidot, A. Berchanski and G. Borkow, Insight into the Mechanisms of Aminoglycoside Derivatives Interaction with HIV-1 Entry Steps and Viral Gene Transcription , FEBS J., 2008, 275, 5236. 

Nehramyo in and related aminoglycoside derivatives (D 24). These cimino sugar derivatives are classified in three series which are character-iszed by typical structural units I (apramycin, oxyapramycin), II (kanamycin B, tobramycin) and III (nebramine, lividamine, neamine). 

Scheme 16.7 Synthesis of aminoglycoside derivative 22 using azides as proteaing groups for amines. First, the amino groups of 18 were converted into azides by diazo transfer.After chemical remodeling of the aminoglycoside (one amino group was replaced by a hydroxy group), the amines were regenerated by Staudinger reduction ...

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