Lividomycin preparation

Neomycins, Paromomycins, Lividomycins. Although the tetra- and pen-tacyclic aminoglycosides have been known for some time (neomycin 1949, paromomycin 1959, lividomycin 1967), only a few chemical modifications have been carried out. Not until after the discovery of the enzymatic inactivation mechanisms were several deoxy compounds and acylated derivatives (HABA, etc.) prepared. 

Deoxy- and 6 -5"-dideoxyparomomycin 143, 144 were prepared from the pen-ta-N-benzyloxycarbonylparomomycin by reaction with tosylchloride, after separation of the two intermediates 6 -tosyl- and 6, 5"-ditosylparomomycin and subsequent reduction The importance of the 5"-hydroxyl group within the ribose containing aminoglycoside antibiotics (see ribostamycin) has been demonstrated by suitable modifications of lividomycin. 

The structure, lividomycin 5"-phosphate, was furthermore proved by chemical synthesis. Penta-N-(benzyloxycarbonyl) lividomycin A was prepared from lividomycin A by the usual Schotten-Baumann procedure in a yield of 95% it had m.p. 135-150° (dec.). Acetonation with 2,2-dimethoxypropane in N,N-dimethylformamide in the presence of p-toluenesulfonic acid at 110° for 4 hours afforded the tri-O-isopropylidene derivative of N-(benzyloxycarbonyl)lividomycin A in 49% yield m.p. 129-133° (dec.). Phosphorylation of the sole primary hydroxyl group in the D-ribose moiety of -(benzyloxycarbonyl) lividomycin A with diphenyl phosphorochloridate in dry pyridine gave penta-N-(benzyloxy-... 

B (517) has also been synthesized from ribostamydn by introducing the 3 -deoxy and N -[(S)-4-amino-2-hydroxybutyryl] groups. Neomydn and paromomycin have been converted into their 5"-amino-5"-deoxy analogues, via the corresponding 5"-bromides, and 3 -deoxyparomamine (available by hydrolysis of lividomycin) has been transformed, by way of the action of nitromethane on its 6 -aldehyde derivative, into isomeric 6 -C-aminomethyl-3 -deoxyparomamines (519). The use of the Tipson-Cohen procedure to prepare 3, 4 -unsaturated derivatives of butirosin and kanamycin is mentioned in Chapter 12. 

Periodate oxidation of derivatives of neomycin B, parmomomycin, and lividomycin B followed by base-catalysed )S-elimination of the oxidized units has been used to obtain constituent pseudo-di- and -tri-saccharides of these antibiotics. 5-Epi, 6-epi-, and 5,6-diepi-neamine have been prepared from appropriate neamine derivatives by standard sequences involving glycosulose or oxiran intermediates. ... 

Deoxy-5"-fluoro-lividomycin has been prepared using the DAST... 

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