A-21978C cyclic peptides of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, an amino-protecting group, 8-methyldecanoyl, 10-methylundecanoyl, 10-methyldodecanoyl, the specific C10 -alkanoyl group of A-21978C factor C0 and the specific C12 -alkanoyl groups of A-21978C factors C4 and C5 ; R1 and R2 are, independently, hydrogen or an amino-protecting group, and salts thereof, are prepared by enzymatic deacylation of an antibiotic selected from A-21978C complex, A-21978C factors C0, C1, C2, C3, C4 amd C5 and blocked A-21978C complex and factors C0, C1, C2, C3, C4 and C5, using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. The A-21978C cyclic peptides and salts thereof are useful intermediates to prepare new semi-synthetic antibacterial agents.

A-21978C cyclic peptides

This invention concerns the recovery of glycopeptidic antibiotics from aqueous solutions resulting from fermentation broths or process streams. Examples of glycopeptidicantibiotics to which the process of this invention may be applied are the following: vancomycin, actaplanin, ristocetin, avoparcin, actinoidin, LL-AM-374, A 477, OA 7653, A 35512 B, A 515668, AAD 216, A 41030, A 47934, A-40926 (European Pat. Appln. No. 85112406.5), the individual factors, derivatives and pseudo-aglycones and aglycones thereof, teicoplanin and teicoplanin-like compounds.

A process for recovery of glycopeptidic antibiotics

An improvement in the large-scale recovery of vancomycin-type glycopeptide antibiotics which comprises (1) commingling the fermentation medium in which the antibiotic is produced with a polystyrene divinylbenzene resin such as Dow XFS-43278.00, (2) separating the resin from the medium and (3) eluting the antibiotic from the resin. This improvement avoids preliminary filtration and pH adjustment of the broth, simplifies waste-disposal problems and eliminates antibiotic losses due to mycelial adsorption and filtration.

Glycopeptide recovery process

A-21978C cyclic peptides of the formula
 wherein R is selected from the group consisting of hydrogen, an amino-protecting group, 8-methyldecanoyl, 10-methylundecanoyl, 10-methyldodecanoyl, the specific C 10 - alkenoyl group of A-21978C factor C o and the specific C 12 -alkanoyl groups of A-21978C factors C 4 and C 5 ; R' and R 2 are, Independently, hydrogen or an amino-protecting group, and salts thereof, are prepared by enzymatic deacylation of an antibiotic selected from A-21978C complex, A-21978C factors C o , C 1 , C 2 , C 3 , C 4 and C 5 and blocked A-21978C complex and factors C o , C 1 , C 2 , C 3 , C 4 and C 5 , using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. These A-21978C cyclic peptides or a pharmaceutically-acceptable salt thereof are useful intermediates for preparing new alkanoyl, alkenoyl, benzoyl, acylamino, N-alkanoylaminoacyl, and alkyl cyclic peptide antibiotics.

Cyclic peptide derivatives

The present invention is directed to ester derivatives at the carboxylic function of the glycopeptidic antibiotic substance called antibiotic L 17046 with antimicrobial activity mainly against gram-positive bacteria.

Ester derivatives of antibiotic l 17046

Antibiotic A-4696 factors B1, B2, B3, C1a, C3, and E1 are isolated from antibiotic A-4696, the latter being produced by Actinoplanes missouriensis strains ATCC 31680, ATCC 31682, and ATCC 31683 under submerged aerobic conditions in a culture medium and isolated from the fermentation broth by absorption on an ion exchange resin and eluted therefrom at pH 10.5 with sodium hydroxide. The novel factors are separated by thin layer chromatography and high pressure liquid chromatography and have antimicrobial and growth promotant activity.

Antibiotic A-4696 factors B1,B2,B3,C1a,C3 and E1

Antibiotic A-4696 factors B 1 , B 2 , B 3 , C 1a , C 3 , and E 1 are isolated from antibiotic A-4696, the latter being produced by Actinoplanes missouriensis strains ATCC 31680, ATCC 31682, and ATCC 31683 under submerged aerobic conditions in a culture medium and isolated from the fermentation broth by absorption on an ion exchange resin and eluted therefrom at p H 10.5 with sodium hydroxide. The novel factors are separated by thin layer chromatography and high pressure liquid chromatography and have antimicrobial and growth promotant activity.

Biologically pure culture of Actinoplanes missouriensis

Glycopeptide antibiotic A-4696G is produced by culturing Actinoplanes missouriensis mutant strain ATCC 31681 under submerged aerobic fermentation conditions, and is recovered from the fermentation broth by resin adsorption and chromatographic purification. A-4696G inhibits the growth of bacteria pathogenic to man and animals and also enhances the growth of ruminants by increasing feed utilization.

Weeks Robert E

Papers

Antibiotic A-4696 factors B1,B2,B3,C1a,C3 and E1

Biologically pure culture of Actinoplanes missouriensis

Antibiotic A-4696 factor G