Dlh

H2N

Compounds 391-395

of fortimicin B [229], the synthesis of 2-amino-3-O-demethyl-2-deoxy- and 3-amino-3-demethoxy fortimicin A [230], and a number of fortimicin analogs modified in the sugar ring, including 4'-hydroxyfortimicin D [231], 7'-C-propylfortimicin A [232], 7'-(3-hydroxypropyl)fortimicin A and its 6'-epimer [233], 7'-phenylfortimicin A and its 6'-epimer [234], and 3'-enofortimicin D [235]. Of these analogs, only 2-amino-3-O-demethyl-2-deoxy- and 3-amino-3-demethoxyfortimicin A showed activity comparable to that of fortimicin A; the others were either inactive or less active than the parent compounds.

Several synthetic methodologies have been employed to convert the 1,6-an-hydromaltose derivative 396 to the 1,4-diaminocyclitol aminoglycoside 397 a fortim-icin analog. However, this compound was approximately 25% as potent as fortimicin A [236]. The same precursor was also used to prepare fortimicin A analogue 398 via regio- and stereoselective introduction of azido and methylamino groups and transformation of the 1,6-anhydrohexopyranose moiety into a cyclitol ring [237] (compounds 396-398 ).

2. Istamycins

3',4'-Dideoxyneamine has been used to prepare demethylated analogs of istamycin A (399). Antibacterial activity screening of these compounds revealed that the 4-N-methyl group is essential for antibacterial activity, since 4-N-demethylated derivatives exhibited weak activity, whereas 6'-N-3-O-didemethylistamycin A still showed activity [238].

The compounds 2"-N-formimidoylistamycin (403) and 2'-N-formimidoylsta-mycin B (404) have been prepared by treatment of appropriately protected istamycin A0 and B0 derivatives with N-ferf-butoxycarbonylglycine (compounds 399-404 ). De-

H9io

"o

0 0

Post a comment