Antibiotics with nucleoside structure

Several relatively recent 13C nmr studies of this class of compounds have been primarily concerned with nucleoside antibiotics (Kreishman et al., 1972 Krugh, 1973 Wenkert et al., 1973 Nouaille et al., 1974 Dca et al., 1974). The structure and conformation of... 

The isolation of a product identical with psicofuranine was simultaneously reported by Yiintsen who had named his product angustmycin C. Structure studies showed that it, too, is 9-D-psicosyladenine. Yiintsen and and Yonehara also isolated another nucleoside-like product which they called angustmycin A and for which they derived structure (31). Hydrolysis of the antibiotic with a strong acid permitted isolation of the adenine, but... 

A recently developed application of the Ramberg-Backlund reaction is the synthesis of C-glycosides. The required thioethers can be prepared easily by exchange with a thiol. The application of the Ramberg-Backlund conditions then leads to an exocyclic vinyl ether that can be reduced to the C-nucleoside.95 Entries 3 and 4 in Scheme 10.6 are examples. The vinyl ether group can also be transformed in other ways. In the synthesis of partial structures of the antibiotic altromycin, the vinyl ether product was subjected to diastereoselective hydroboration. 

Nucleocidin (LXXX) [353], an adenine nucleoside antibiotic whose structure has recently been elucidated, is also a potent inhibitor of protein synthesis. Studies with this compouna have led to the conclusion that nucleocidin forms a complex with ribosomes which is inactive in peptide bond formation. Binding... 

The discovery of the polyoxin group (1) of antifungal nucleoside antibiotics (2) spurred the attention of synthetic chemists as well as biologists for a number of reasons. Their unusual structural features combined with unique biological activity fostered studies on many fronts (3). During their studies on the biosynthesis of the polyoxins, Isono, Crain and McCloskey (4) discovered three novel acidic nucleosides which they called octosyl acid A, B and C,... 

The trans-fused perhydrofuropyran system is also encountered in the ezomycin group of nucleoside antibiotics (6,7). The structures of ezomycin Aj and Aj are shown in Figure 3 for comparison with the octosyl acids. 

Amicetin, the first nucleoside in a series of structurally related, antibiotic substances isolated from Streptomyces cultures, was shown to possess antituberculous activity.9 Proof of the main structural features of this rather complex nucleoside (XXXIV) represents an interesting example of the use of degradative procedures coupled with periodate oxidations, spectrophotometric methods, and potentiometric titrations163-167 (see XXXIV-XL). 

Unlike the (3-lactones and (3-lactams, the mode of action of the unusual C-glucosyl nucleoside-based natural product showdomycin is unknown. Nevertheless, this compound has been shown to possess potent antibiotic properties, with results obtained in vitro suggesting a role as a suicide inhibitor of uridine metabolism [11]. Isolated from the bacteria Streptomyces showdoensis, showdomycin contains an electrophilic moiety, malaimide, in place of the base (cf. the structures of uridine or pseudouridine). 

Fig. 4.11 Chemical structures of antibiotics. Chemical structures of nucleosides are provided in the top row for comparison with the antibiotics shown in the second row. The third row shows chemical structures of antibiotics that only weakly resemble the nucleosides to which they have been compared.

The prototypical aminoacylated nucleoside analogue antibiotic is puromycin which inhibits the protein translation in all three domains of life. The chemical structure of puromycin is the same as that of tyrosylated adenosine, except for the presence of three added methyl groups and the replacement of an ester bond with an amide bond (Fig. 4.11). Puromycin mimics tyrosyl-tRNA so well that it binds to the A-site and gets incorporated into an elongating peptide. This leads to termination of translation because puromycin terminated peptides fall off the ribosome. Puromycin derivatives have been used crystallographically as peptidyl transferase substrates and have contributed to our understanding of the structure of the peptidyl transferase site (Fig. 4.5) [11, 16, 45],... 

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