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Opening of the aziridine ring of 2-deoxy-1,2-epimino-2- epi -fortimicin B ( 10 ) has been effected with both chloride and azide. The reactions are both stereo- and regiospecific and give 2-chloro-2-deoxyfortimicin B ( 2c ) and 2-azido-2-deoxy-fortimicin B ( 2d ). The nucleophilic displacements of the methanesulfonate groups of some 1- N -benzyloxycarbonyl-2- O -(methylsulfonyl)fortimicin derivatives with chloride, azide, and cyanide in N,N -dimethylformamide are dependent both on the nature of the nucleophile and the specific 1- N -benzyloxycarbonyl-2-methanesulfonate employed as the substrate. Striking differences in the stereochemistry of the azide displacements with different 2-methanesulfonates are believed to have a conformational basis. 2-Amino-2-deoxyfortimicin A ( 1c ) and both of the 2-epimeric 2-chloro-2-deoxyfortimicins A ( 1b ) and ( 5 ) were prepared for antibacterial assay and the in vitro results are reported.

The preparation of 4-de-N-methylfortimicin A analogs as well as the preparation of 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B is reported. It was shown that the 4-N-methyl group in fortimicin analogs is essential for antibacterial activity since neither the 4-de-N-methylfortimicin A nor the 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B exhibited useful biological activity.

Preparations of 2- epi -fortimicin A ( 4 ) from 2- epi -fortimicin B ( 3 ) are described. In contrast to the previously reported, selective 4- N -acylation of 1,2′,6′-tri- N -benzyloxycarbonylfortimicin B ( 8 ) with N -( N -benzyloxycarbonylglycyloxy)succinimide, 1,2′,6′-tri- N -benzyloxycarbonyl-2- epi -fortimicin B ( 5 ) underwent predominant 2- O ,4- N -diacylation under similar conditions. Proof of the structure of the diacylated product is presented, with evidence that the diacylated product is formed by initial intramolecular, base-catalyzed 2- O -acylation. The in vitro antibacterial activities of 2- epi -fortimicin A ( 4 ), 2- O -glycyl-2- epi -fortimicin A ( 11 ), 1- N -glycyl-2- epi -fortimicin A ( 12 ), and 5-deoxy-2- epi -fortimicin A ( 13 ) are reported.

Attempted removal of the 3'-hydroxyl group of seldomycin factor 5 via displacement of a sulfonate ester has led to 3'-epi-seldomycin factor 5. Removal of the hydroxyl group has been effected by the Barton procedure. The antibacterial activity of 3'-epi- and 3'-deoxyseldomycin factor 5 against various aminoglycoside-resistant strains is discussed.

Synthesis of 2-epi-fortimicin B has been accomplished by processes involving solvolyses of both 1-N-benzyloxycarbonyl- and 1-N-acetyl-2-O-(methylsulfonyl)fortimicins B, which occur with participation of the carbonyl oxygen atoms of the 1-N-acyl groups. The results illustrate both the greater effectiveness of acetamido groups in neighboring-group participation relative to benzyloxycarbonylamino groups, and the sensitivity of the nature of the products to the reaction conditions.

The preparations of 4-N-glycyllysinomicin and several 4-N-aminoacyl derivatives of compounds prepared from lysinomicin are presented. The new substances have lower antimicrobial activities than the original 4-N-unsubstituted lysinomicin derivatives. This result indicates that the structure-activity relationship observed with fortimicin A and fortimicin B does not apply to the lysinomicin derivatives studied.

7-Deoxy-4(R)-dihydrospectinomycin (7) has been prepared and its structure firmly established by proton magnetic resonance and high resolution mass spectrometry. This spectinomycin analog is devoid of antibiotic activity.

The structures of fortimicins A and B have been determined by PMR, CMR, mass spectra and CD combined with chemical degradations. Both antibiotics are pseudodisaccha-rides and incorporate a novel aminocyclitol, fortamine. Incontrast to the diaminocyclitol moieties of known aminoglycosides, fortamine is a 1, 4-diamine, contains both N- and O-methyl groups and possesses chiro stereochemistry. Both antibiotics are glycosides of 6-epi-pur-purosamine B, but fort imicin A differs from fortimicin B by being a glycyl amide.

The structures of seldomycin factors 1 and 2 have been determined by consideration of chemical degradation and spectral properties. Factor 1, also known as XK-88-1, is shown to be 6-O-(2-amino-2-deoxy-alpha-D-xylopyranosyl) paromamine (1) and factor 2, also known as XK-88-2, is shown to be 4'-deoxy-neamine (2). Mass spectral evidence has been obtained that suggests the most probable structure for seldomycin factor 3, also known as XK-88-3, is 6'-amino-6'-deoxyseldomycin factor 1 (12).

Selective 6'-N-alkylation of 1, 2'-di-N-benzyloxycarbonylfortimicin B was effected by both catalytic and chemical reductive alkylation in the presence of aldehydes. These facile selective 6'-N-alkylations were used as the basis of the preparations of the 6', 6'-di-N-methylfortimicins A and B, and the 6'-N-methylfortimicins A and B. Of these new 6'-N-methylated fortimicins, only 6'-N-methylfortimicin A has appreciable antibacterial activity, which was about half that of fortimicin A.

The preparation of 1, 2-anhydro-2', 6'-di-N-benzyloxycarbonyl-1 -deaminofortimicin B-4, 5-carbamate (4) and its conversion to the two diastereomeric 2', 6'-di-N-benzyloxycarbonyl-1-deamino-2-deoxy-1, 2-epoxyfortimicin B-4, 5-carbamates 7 and 13 are described. The olefin 4 was used for preparation of 1-deamino-2-deoxyfortimicin A (6d) while the β-epoxide 13 was used for the preparation of 1, 2-di-epi-fortimicin A (17b) and 2-amino-1-deamino-2-deoxy-1-hydroxyfortimicin A (19c). The in vitro antibacterial activities of 6d, 17b and 19c are reported.

7-Epi-spectinomycin (9) and 7-epi-4(R)-dihydrospectinomycin (10) have been prepared and their structures firmly established by proton magnetic resonance. Both of these spectinomycin analogs are devoid of antibiotic activity.

The conversion of fortimicin E, a minor metabolite from the Micromonospora olivoasterospora fermentation which also produces fortimicin A and fortimicin B, to four 4-N-aminoacylfortimicins E was accomplished. The new 4-N-aminoacylfortimicins E showed only weak antimicrobial activity against several Gram-negative and Gram-positive microorganisms.