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A new aminoglycoside antibiotic, dactimicin produced by a Dactylosporangium matsuzakiense SF-2052 has been isolated by column chromatography on a cation-exchange resin and CM-sephadex. The structure of dactimicin was determined to be 4-amino-1,4-dideoxy-3-O-(2,6-diamino-2,3,4,6,7-pentadeoxy-beta-L-lyxo- heptopyranosyl)-1-[(N-formimidoylglycyl)-methylamino]-6-O-methyl-L-chiro-inosit ol. Alkaline hydrolysis of dactimicin afforded 1-N-(N-formylglycyl)fortimicin B, fortimicin B, fortimicin A and an acyl migration product, 2'-N-(N-formylglycyl)fortimicin B.

Dactimicin is a new member of the pseudodisaccharide group of antibiotics. It possesses an unusual N-formimidoyl group which differentiates it from astromicin. Dactimicin is active against wide variety of bacteria, including resistant strains with aminoglycoside-modifying enzymes. However, AAC(3)-I enzyme slowly acetylates dactimicin. Animal toxicity studies show that the ototoxicity and nephrotoxicity of dactimicin are lower than those of amikacin and gentamicin. No notable abnormal findings have been found in pharmacological and toxicological studies.

Treatment of 9,2'-diacetylmidecamycin (2) with DMSO and acetic anhydride afforded 3''-methylthiomethyl derivative (3) preferably in the presence of pyridine. Reaction of midecamycin (1) with DMSO and acetic anhydride gave 2'-acetyl-9-dehydro-3''-methylthiomethyl derivative (9) indicating that the three hydroxyl groups reacted in a different way to the reagent. When compound 2 was reacted with DMSO and acetic anhydride in the presence of CCl4, 3''-acetoxymethyl derivative (13) was a major product, which was formed via 3 through the Pummerer rearrangement. The structures of 3, 9 and 13 were confirmed by examining NMR and mass spectra of these compounds and their deuterio analogue. They showed antimicrobial spectra similar to 1 but superior in vivo activity.

ME2303 (FAD-104) is a new anthracycline antibiotic whose structure is characterized by the presence of a 2'-fluoro atom and the lack of a 3'-amino group in the sugar moiety. Its cytocidal activity is superior to or equal to that of adriamycin (ADM). The LD50 value of ME2303 was about 140 mg/kg i.v. in mice and this value was about 7-fold higher than that of ADM. ME2303 was administered intravenously to Golden strain hamsters at doses of 25, 50, 75 and 150 mg/kg and the ECG was examined. From ECG changes, it seems that ME2303 did not show any effect on the heart in acute toxicity. Mutagenicity was recognized as with ADM in the back-mutation test.

N-Carbamoyl-D-glucosamine was isolated from the culture of Streptomyces halstedii SF-1993. It showed weak antimicrobial activity against some Gram-negative bacteria and some fungi.

C-7 and C-3 substituents of a new antibiotic SF-1623 were chemically modified to improve the bioactivity, and substituent effect at C-7 and C-3 was examined on the basis of MIC and ED50 values against selected bacteria. Among a large number of derivatives, MT-141 possessing 2-D-2-amino-2-carboxyethylthioacetamido residue at C-7 and N-methyltetrazolyl-thiomethyl residue at C-3 showed a high order of antibacterial activity in vitro and especially in vivo.

9,3''-Diacetylmidecamycin (12) was synthesized from 4''-depropionyl-9,2',4''-triacetylmidecamycin (8) by heating the latter with propionic anhydride in pyridine followed by removal of 2'-acetyl group, with or without 18-enolpropionyl group. Direct acetylation of midecamycin (1) led to the formation of the 3'',4''-positional isomer (6). The structure of 12 was determined by mass, NMR and chemical degradation. The location of 3''-acetyl group was shown by the stereospecific 3 leads to 1 acetyl migration catalyzed by a base of 3-O-acetyl-4-O-propionyl-L-mycarose (13), and comparison of NMR and mass fragmentation with the 3,4-positional isomer (15). The latter's structure was independently supported by the nuclear Overhauser effect between methyl and propionyl group at C-3. The intramolecular 4 leads to 3 acyl shift that was taken place in the forced acylation of the mycarose moiety was found to be affected by the anomeric configuration, nature of aglycones and reaction temperature. Reverse 3 leads to 4 acyl migration occurred in acidic hydrolysis.