H2n

Sporaricin A 407 R1 = H, R2 = OMe of 3-demethoxysporaricin A [246], as well as 5-deoxy-5-fluorosporicin A [247]. In this work, the direct fluorination method was used with the DAST reagent to make the fluorinated analogs.

4. Lysinomicin

4-N-Glysyllysinomicin (415) and several 4-N-aminoacyl analogs of lysinomicin derivatives (compounds 416-418) have been prepared to examine the effect of 4-N-aminoacylation on antibacterial activity of this class of aminoglycoside antibiotics (compounds 414-418 ). In contrast to lysinomicin, which is slightly more potent than fortimicin A (372), the new analogs showed lower activity than the 4-N-unsubstituted lysinomicin derivatives, indicating that the structure-activity relationship observed with fortimicins does not apply to lysinomicin derivatives [248].

5. Sannamycins

Ludin et al. [249] have described the synthesis of the pseudodisaccharide sannamycin 419, its 2-epimer, and a variety of other isomers including the enantiomers of san-namycin. These workers also prepared various other sannamycin analogs including 6'-de(N-methyl) sannamycin A (420) and its 2'-epi isomer 421, as well as derivatives 422 and 423, using the glycosyl donors 424 or 425 for glycosylation with sannamine-type glycosyl acceptor 426 (compounds 419-426 ).

Among these analogs, compound 420 showed no activity, and 421 was slightly active, but much less active than the parent compound, sannamycin (419) [250].

I. Other Aminocyclitol Aminoglycosides

Three a-glycosidase inhibitors of 2,5,6-trideoxystreptamine (compounds 427-429) have been prepared by glycosylation of the quinic acid derived ditosyloxycyclo-hexanol derivative 430, with the corresponding glycal derivatives (e.g., 431 and 432)

Lysinomicin 414 R1 = H, R2 = COCH2CH(NH2)(CH2)3NH2

415 R1 = COCH2NH2, R2 = COCH2CH(NH2)(CH2)3NH2

0 0

Post a comment