Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Kirin Beer Kabushiki Kaisha

Microbial Chemistry Research Foundation

Sanraku Incorporated

Hamao Umezawa, Deceased

Tomio Takeuchi

Kuniaki Tatsuta

Masaaki Ishizuka

Teruya Nakamura

Yoshiro Okami

Yoji Umezawa, Heir

Shinichi Kondo

Atsushi Takahashi

Akio Fujii

Yoshikazu Takahashi

Takaaki Aoyagi

Shunzo Fukatsu

Tomoyuki Ishikura

Katsutoshi Takahashi

Tetsushi Saino

Daishiro Ikeda

Tsuyoshi Inoue

Akihiro Yoshimoto

Tsutomu Sawa

Fuminori Abe

Shohachi Nakajima

Hiroyuki Kawai

Yoshio Watanabe

Osamu Jodo

Masaya Imoto

Kunio Isshika

Yoshiro Okamo, Heir

Toshiyuki Kamayama

Shogo Kurasawa

Masao Yoshida

A DNA segment of this invention is a DNA fragment of a length of about 3.8 kb which is obtained by excising with a restriction endonuclease Bgl II a hybrid plasmid pST 141 having a length of about 12.6 kb of Streptomyces griseus 4-1 strain (FERM P-7984, namely, FERM BP-1198) to give a Bgl II-Bgl II DNA fragment, and then excising with a restriction endonuclease Sph I the resultant Bgl II-Bgl II DNA fragment having a length of about 7.0 kb and having the restriction endonuclease sites as shown in the restriction endonuclease map of FIG. 1 . This DNA fragment is a DNA which contains a streptomycin resistance gene and contains, in the vicinity of this gene, such a DNA region possessing a function to control the expression of the streptomycin resistance gene. An insertion of this DNA fragment having a length of about 3.8 kb into a suitable actinomycetes plasmid vector can produce such a hybrid plasmid which acts reliably as a selected marker of the streptomycin resistance.

DNA segment containing streptomycin resistance gene and being capable of

The present invention relates to novel Spergualin-related compounds represented by the general formula [I] ##STR1## (wherein X is ##STR2## R is --H or --CH.sub.2 OH; R.sub.1 is --H, ##STR3## R.sub.2 is a residue obtained by removing, from an amino acid or peptide, the hydroxyl group of the carboxyl group and, when R.sub.1 is a group other than --H, R.sub.2 is same as R.sub.1), or a pharmacologically acceptable salt thereof. Said compounds or salts thereof have an immuno-modulating action.

Novel spergualin-related compounds and process for producing the same

The present invention provides new physiological active substance erbstatin analogue compounds of a general formula (I), which have excellent tyrosine-specific protein-kinase inhibitory activity, antitumor activity and antimicrobial activity. ##STR1## (in which R.sup.1 represents a hydrogen atom, a lower alkanoyl group or a lower alkyl group; n represents a positive integer of 1 to 3;

Physiologically active erbstatin analogue compounds and compositions

New anthracycline antibiotics of a formula (I) are provided, which are usable as an anticancer agent ##STR1## (where R represents a hydrogen atom or a hydroxyl group). The antibiotics (I) can be produced by incubation of a dye-nonproductive or hardly dye-productive mutant strain which has an ability of converting .alpha.-citromycinone or .beta.-isorhodomycinone into the antibiotics (I), in the presence of .alpha.-citromycinone or .beta.-isorhodomycinone in a pertinent nutrient medium.

Anthracycline antibiotics DCP-1 and 2

Disclosed is a process for producing a 10-hydroxyanthracycline of the following formula (II) which comprises reacting a compound of the following formula (I) or an acid addition salt thereof with an N-oxide of a tertiary amine ##STR1## wherein: R.sup.1 through R.sup.6 each designate any of H, OH and OCH.sub.3 ; R.sup.7 designates any of H, OH and a sugar residue; and R.sup.8 designates any of C.sub.2 H.sub.5, COCH.sub.3, CH(OH)CH.sub.3, CH(OH)CH.sub.2 (OH) and COCH.sub.2 OH. In accordance with this process, it is possible to efficiently introduce a hydroxyl group into the 10-position of an anthracycline having no substitutent at the same position thereof.

Process for producing 10-hydroxyanthracyclines

A novel compound having anti-tumor activity is disclosed which is 1,12-dihydroxy-1,6,12,17-tetraazacyclodocosan-2,5,13,16-tetrone produced microbiologically by culturing a microorganism belonging to the genus of Alteromonas or, in particular, Alteromonas haloplanktis SB-1123. The characterization data of the compound and the microbiological properties of the microorganism are described. The results of in vitro assays are given for the anti-tumor activity of the compound against L-1210 and IMC carcinoma cells.

Bisucaberin

Known compound, optically active arphamenine A can now be synthesized in an optically active pure form and in a favorable yield by a new process comprising consecutive steps with starting from L-arginine, wherein racemization of intermediate reaction products can be minimized.

Synthesis of arphamenine A

The present invention relates to an immunosuppressing method which comprises administering a spergualin-related compound represented by the following formula ##STR1## (wherein R.sub.1 is --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.6 --, ##STR2## R.sub.2 is --(CH.sub.2).sub.2 -- or --CH.dbd.CH--; and R.sub.3 is ##STR3## or pharmacologically acceptable salts thereof in an effective amount to a warm-blood animal.

Immunosuppressing method

For the preparation of 4'-0-tetrahydropyranyladriamycin b, the 9,14-position of the starting adriamycin is previously protected with phenylboronic acid and then the 4'-position of the thus protected adriamycin is selectively tetrahydropyranylated. After the tetrahydropyranylation, the by-product of 4'-0-tetrahydropyranyladriamycin a is converted to the aimed product of 4'-0-tetrahydropyranyladriamycin b. The yield of the product of 4'-0-tetrahydropyranyladriamycin b is high. The present invention provides a method for the preparation of 4'-0-tetrahydropyranyladriamycin b, where 3,4-dihydro-2H-pyran is added to a reaction solution containing a 9,14-protected adriamycin as obtained by (a) reacting adriamycin and phenyl-boronic acid or (b) reacting 4'-0-tetrahydropyranyladriamycin b and phenylboronic acid in the presence of an acid catalyst, for 4'-tetrahydropyranylation of the said 9,14-protected adriamycin, and then, the 9,14-protected position of the resulting product is deprotected and 4'-0-tetrahydropyranyladriamycin b is isolated by chromatography with silica-gel.

Method for the preparation of 4'-0-tetrahydropyranyladriamycin b

As new 2'-deamino-2'-hydroxyistamycin B.sub.o derivatives are provided four compounds, namely 2'-deamino-2'-hydroxyistamycin B; 2'-deamino-2'-hydroxy-3-O-demethylistamycin B; 4-N-(.beta.-alanyl)-2'-deamino-2'-hydroxyistamycin B.sub.o ; and 4-N-(.beta.-alanyl)-2'-deamino-2'-hydroxy-3-O-demethylistamycin B.sub.o which all exhibit high antibacterial activity and low acute toxicity in combination. These new compounds are useful as antibacterial agent.

2'-deamino-2'-hydroxyistamycin B.sub.o derivatives of low toxicity

Growing community of inventors

Tokyo, Japan

Hamao Umezawa, Deceased