Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Sanraku-ocean Co., Ltd.

Bristol-myers Company

Taiji Inui

Hamao Umezawa

Tomio Takeuchi

Toshikazu Oki

Hiroshi Naganawa

Masaaki Ishizuka

Masa Hamada

Takaaki Aoyagi

Akihiro Yoshimoto

Akira Takamatsu

Kageaki Kouno

Norio Shibamoto

Hiroshi Tone

Rokuro Okamoto

Hajime Morishima

Yoshiaki Yagi

Yasue Matsuzawa

Hajime Morishama

Masaaki, All Ishizuka

Shunro Mori

New anthracycline compounds, 2-hydroxyaclacinomycin A having potent antitumor activity and lower toxicity, 2-hydroxyaklavinone as an useful precursor for producing anthracycline glycosides, and a process for the production thereof by microbial conversion method are disclosed.

2-Hydroxyaclacinomycin A and 2-hydroxyaklavinone and process for

The invention is to provide a new process for producing daunomycin and baumycins having potent antitumor activity and low toxicity by microbial conversion of anthracyclinones such as aklavinone and .epsilon.-rhodomycinone.

Process for producing anthracycline glycosides

This invention provides tetrapeptide derivatives of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are methyl, 1-methylethyl, 2-methylpropyl, 1-hydroxyethyl, 2-carboxyethyl or 4-aminobutyl and Y is ##STR2## wherein R.sup.3 is methyl, 1-methylethyl, 2-methylpropyl, 1-methylpropyl, hydroxymethyl, 1-hydroxyethyl, carboxymethyl, 2-carboxyethyl, 4-aminobutyl, 3-guanidinopropyl, benzyl or p-hydroxybenzyl excluding the compounds in which R.sup.1 and R.sup.2 are each 1-methylethyl and also R.sup.3 is carboxymethyl or 2-carboxyethyl, the first and leftmost .beta.-amino acid moiety in said tetrapeptide derivatives having the (2S,3R)-configuration and a primary amino group and the second, third and fourth .alpha.-amino acid moieties in said tetrapeptide derivatives having the L-configuration. These compounds have an inhibitory activity on several types of aminopeptidases.

Physiologically active tetrapeptides

A process for producing cyclodextrins which comprises using cultured medium of the strains belonging to genus Micrococcus, filtrate thereof or enzyme preparation obtained therefrom, especially, the process in which the ratio of .alpha.-cyclodextrin to .beta.-cyclodextrin can be desirably varied by regulating the condition of the reaction mixture, is disclosed.

Process for producing cyclodextrins

New anthracycline glycoside derivatives of rhodomycin-group, .epsilon.-rhodomycin RDC, .epsilon.-isorhodomycin RDC, .beta.-rhodomycin RDC, .gamma.-rhodomycin RDC, .gamma.-rhodomycin RDRs and .beta.-pyrromycin RDC having potent anticancer activities and lower toxicities and a process for the production thereof by microbiological conversion method are disclosed.

Rhodomycin antibiotics

New anthracycline derivatives, 1-hydroxy-13-dihydrodaunomycin and N-formyl-1-hydroxy-13-dihydrodaunomycin are produced by microbial transformation of .epsilon.-pyrromycinone and .epsilon.-isorhodomycinone with daunomycin-producing streptomyces and their mutants. The derivatives herein are useful as cancer chemotherapeutic agents.

Anthracycline derivatives and process for preparing the same

New anthracycline glycosides designated MA 144-G1, -G2, -L, -S1, -N1, -U1 and -Y which inhibit the growth of gram-positive bacteria and mammalian tumors are produced by fermentation of certain species of Streptomyces and by the chemical or enzymatic conversion of certain anthracycline glycosides. New microbiological and chemical processes are also provided for preparation of the anthracycline glycosides MA 144-S2 and -U2 which have been found to be identical with the previously reported anthracyclines, marcellomycin and musettamycin.

Method of producing anthracycline antibiotics

New antitumor agents designated MA 144-M.sub.1 and MA 144-M.sub.2, which are anthracycline glycosides and inhibit the growth of gram-positive bacteria, e.g. Staphyococcus aureus, Bacillus subtilis and Sarcina lutea, and inhibit the growth of animal tumors such as leukemia L 1210, P 388 and sarcoma 180 are produced by fermentation of MA 144-producing strains of streptomyces and by the chemical or enzymatic conversion of aclacinomycin A or cinerubin A.

Process for producing antibiotics MA 144-M.sub.1 and MA 144-M.sub.2

New anthracycline glycosides designated MA 144-G1, -G2, -L,-S1, -N1, -U1 and -Y which inhibit the growth of gram-positive bacteria and mammalian tumors are produced by fermentation of certain species of Streptomyces and by the chemical or enzymatic conversion of certain anthracycline glycosides. New microbiological and chemical processes are also provided for preparation of the anthracycline glycosides MA 144-S2 and -U2 which have been found to be identical with the previously reported anthracyclines, marcellomycin and musettamycin.

Process for producing new antitumor anthracycline antibiotics

New anthracycline glycosides designated MA 144-G1, -G2, -L, -S1, -N1, -U1 and -Y which inhibit the growth of gram-positive bacteria and experimental animal tumors are produced by fermentation of certain species of Streptomyces and by the chemical or enzymatic conversion of certain anthracycline glycosides. New microbiological and chemical processes are also provided for preparation of the anthracycline glycosides MA 144-S2 and -U2 which have been found to be identical with the previously reported anthracyclines, marcellomycin and musettamycin.

Anthracycline antibiotics

A number of 4'-acyl derivatives of tylosin and acetyltylosin which are prepared by first protectively acylating at the 2'-hydroxyl group of tylosin or acetyltylosin, secondly at the 4''-hydroxyl group thereof, thirdly at the 4'-hydroxyl group thereof and finally deacylating the 2'- and 4''-acyl groups to produce new 4'-acyl derivatives of tylosin or acetyltylosin which effect high blood level compared to those tylosin derivatives heretofore are disclosed.

Tylosin derivatives

New antitumor agents designated MA 144-M.sub.1 and MA 144-M.sub.2, which are anthracycyline glycosides and inhibit the growth of gram-positive bacteria, e.g. Staphyococcus aureus, Bacillus subtilis and Sarcina lutea, and inhibit the growth of animal tumors such as leukemia L 1210, P 388 and sarcoma 180 are produced by fermentation of MA 144-producing strains of streptomyces and by the chemical or enzymatic conversion of aclacinomycin A or cinerubin A.

Process for preparing antibiotics MA 144-M.sub.1 and MA 144-M.sub.2

A novel anthracycline antibiotic complex designated herein as baumycin complex is produced by fermentation of a baumycin-producing strain of Streptomyces, e.g. Streptomyces coeruleorubidus ME 130-A4 (FERM-P3540, ATCC 31276). The complex and four bioactive components thereof designated baumycin A.sub.1, A.sub.2, B.sub.1 and B.sub.2 are useful as antibacterial and antitumor agents.

Process for producing antibiotic baumycin complex and components

New antitumor agents designated rhodirubin A and B, which are anthracycline glycosides and inhibit the growth of gram-positive bacteria and mammalian tumors, are produced by fermentation of rhodirubin-producing strains of Streptomyces, e.g. Streptomyces sp. ME 505-HEI (ATCC 31273).

Growing community of inventors

Chigasaki, Japan

Taiji Inui