Nh

R2voh

Compounds 307-312

arbekacin free base. Some of these compounds showed MIC as low as 0.10 mg/mL against S. aureus [155].

2. Gentamicins

An extensive report by a group from the Schering-Plough Corp., describes the synthesis of a series of hexopyranosyl, hexofuranosyl, pentopyranosyl, and pentofura-nosyl derivatives of gentamicin C1 and C1a with general formula of 314 [156,157]. The same group also prepared several 1- or 3-substituted and 1- or 3-e^i-substituted

Arbekacin Compound 313

analogs of sisomicin and gentamicin (e.g., 315-324). These compounds were synthesized from the corresponding 1- and 3-oxo derivatives by suitable reductive techniques, and the oxo compounds themselves were prepared from selectively protected gentamicin and sisomicin derivatives by means of the Corey procedure, using 3,5-di-ferf-butyl-1,2-benzoquinone for deamination-oxidation. The 1-hydroxy, 1-epi-hy-droxy, 1-alkylamino, and 1-epi-alkylamino derivatives (compounds 316, 317, 320, and 321 respectively) were all highly potent antibiotics, and epimerization at the 1-position has not significant effect on biological activity. On the other hand, the 3-hydroxy, 3-epi-hydroxy, and 3-epi-amino derivatives were essentially devoid of any antibacterial activity [158]. Likewise, a number of 1-V-carbonyl derivatives of gen-tamicins, sisomicin, and kanamycin A, including amino and thio analogs with the general formula (partial structure) of 325 (compounds 314-325 ), have been synthesized. Some of these, particularly the 1-V-aminoalkoxycarbonyl and 1-V-aminoal-kylcarboxamido analogs, exhibited highly potent antibacterial activity [159].

In another report, by Paulson and Jansen [160] described synthesis of the sisomicin analog 328 by glycosylation of the suitably protected disaccharide 326 with furanosyl bromide 327 in the presence of mercury cyanide. Likewise, gentamicin X2 analogs (compounds 329-331) were prepared by glycosylation of an appropriate 2-azido-glycosyl chloride with a garosaminyl-deoxystreptamine derivative. The antibacterial activity screening showed no activity for 330 and 331 [161]. The same group has also reported the synthesis of the tetra-V-acetylsisamine 333 (compounds

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