Meiji Seika Kaisha, Ltd.

Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Shigeo Seki

Shunzo Fukatsu

Fumio Kai

Satoru Nakabayashi

Shokichi Nakajima

Toshinori Saito

Hamao Umezawa

Sumio Umezawa

Shuntaro Yasuda

Hitoshi Ikeda

Taro Niida

Masao Koyama

Yujiro Yamada

Ken Nishihata

Nobuo Itoh

Shinichi Kondo

Takashi Tsuruoka

Shigeharu Inouye

Seiji Shibahara

Katsuyoshi Iwamatsu

Hideaki Takahashi

Tetsuro Watanabe

Shigeharu Inoue

Tomizo Niwa

Yasuharu Sekizawa

Masahiro Onodera

Toshio Yoneta

Takemi Koeda

Michiaki Iwata

Chuhei Nojiri

Osamu Makabe

Yuzo Kazuno

Shinji Miyado

Keinosuke Miyauchi

Toshiyasu Ishimaru

Hitoshi Goi

Toyoaki Kawasaki

Yukio Suzuki

Bunzo Nomiya

Shingo Sugimoto

Naotoshi Akai

Yashuharu Sekizawa

Fuguaki Fukuyasu

Yasushi Yusa

Masao Murase

New routes are provided for the synthesis of 3',4'-dideoxykanamycin B which is effective in inhibiting kanamycin-resistant organisms from kanamycin B through new intermediate, of which a fundamental process comprises a new reaction of a 3',4'-epoxy derivative of amino- and hydroxyl-protected kanamycin B with a xanthate to form a corresponding 3',4'-dideoxy-3'-eno derivative followed by removal of the amino- and hydroxyl-protecting groups thereof and by hydrogenation of the resulting 3',4'-dideoxy-3'-eno-kanamycin B. A 3',4'-episulfide derivative corresponding to the 3',4'-epoxy derivative which is formed as second product in the reaction of 3',4'-epoxy derivative with xanthate is also used as intermediate for the preparation of 3',4'-dideoxykanamycin B.

3',4'-Diedeoxykanamycin B derivatives

A 7.alpha.-methoxycephalosporin derivative represented by the formula (I): ##STR1## wherein R.sub.1 represents a heterocyclic ring or an --S-- heterocyclic ring; R.sub.2 represents a hydrogen atom, a carboxy group or a --COOR.sub.5 group wherein R.sub.5 represents a lower alkyl group, a dialkylamino-lower alkyl group or a ##STR2## group wherein R.sub.6 represents a lower alkyl group, a lower acyl group or a lower alkoxycarbonyl group and Y represents a hydrogen atom or a lower alkyl group; R.sub.3 represents a hydrogen atom, a carbamoyl group or a lower acyl group; R.sub.4 represents a hydrogen atom, a lower alkyl group, a dialkylamino-lower alkyl group or a ##STR3## group wherein R.sub.6 and Y are defined as above; A and B, which may be the same or different, each represents a straight chain or branched chain alkylene group having 1 to 5 carbon atoms; and x represents 0 or 1; or a pharmaceutically acceptable salt thereof and a process for producing the same.

7.alpha.Methoxycephalosporin derivatives

4-Amino-2-hydroxybutyric acid or 2,4-diaminobutyric acid may be readily produced by a new process comprising reacting a propionic acid compound containing a .beta.-carboxamido substituent (-CONH.sub.2) on the carbon atom at the 3-position and optionally containing hydroxyl substituent and protected or unprotected amino substituent on the .alpha.-carbon atom thereof, with an alkanoic acid anhydride in liquid pyridine to convert the carboxamido group into a nitrile group, with occasional acylation of a .alpha.-hydroxyl group, occasionally removing the alkanoyl group from the .alpha.-acyloxyl group of the resulting nitrile intermediate, and then reducing the resultant nitrile compound with hydrogen to convert the nitrile group into an aminomethyl group, and further optionally removing the residual amino-protecting group from the resultant 4-aminobutyric acid compound.

Process for the production of 4-aminobutyric acid or its derivatives

Novel cephalosporin derivatives having formulae (V) and (III): ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.8 and A are defined as in the specification.

Cephalosporin derivatives

This invention relates to novel compounds of the general formula (I): ##STR1## wherein A represents ##STR2## in which B represents a ring-forming residue of a 5- or 6-membered carbon-containing heterocycling ring containing at least one nitrogen atom and which may further contain an oxygen atom in the ring, and R.sub.1 and R.sub.2 are the same or different and each represents an alkyl group having from 1 to 6 carbon atoms, a phenyl group, a phenyl group substituted with an alkyl or alkoxy group having from 1 to 4 carbon atoms or a halogen atom, a benzyl group or a benzyl group substituted with an alkyl or alkoxy group having from 1 to 4 carbon atoms or a halogen atom; n represents 0 or an integer of from 1 to 4 corresponding to the number of X substituents; and X represents a halogen atom, a nitro group, a carboxyl group or a carbamoyl group and when two or more X substituents are present they may be the same or different; agents for controlling agricultural and horticultural plant diseases which contain these novel compounds as active ingredients; and to processes for preparing the novel compounds of formula (I).

Agricultural and horticultural pesticides

A novel ester of a cephem compound having a carboxyl group at the 4-position in the nucleus; a process for preparing the same by reacting a cephem carboxylic acid or its salt with a halogenide; and a method for removing the protective group for the carboxyl group in the nucleus of a cephem compound by contacting it with an alcohol, or with an organic solvent in the presence of a Lewis acid.

Polychalcogen ester of cephem compound, process for preparing the same

3',4'-Episulfido kanamycin B compounds

A 9,3'-di-acyl derivative of a macrolide antibiotic can be readily produced by reacting a macrolide antibiotic or an acyl derivative thereof with an organic acid halide, particularly an alkanoic acid halide, in a solvent and in the presence of a molecular sieve consisting of a synthetic zeolite and then de-acylating partially the resultant acylation products by a partial hydrolysis in an aqueous alcohol to give the 9,3'-di-acyl derivative of the macrolide antibiotic.

Process for the production of a 9,3'-di-acyl derivative of a macrolide

A process for preparing a cephalosporanic acid derivative or a 7-acylaminocephalosporanic acid derivative which comprises subjecting an esterifying agent to reaction in liquid sulfur dioxide in the presence of a base with an N-protected-cephalosporin C to obtain a diester, subjecting the diester to reaction in an inert solvent with an iminohalide forming agent to produce an iminohalide, subjecting the iminohalide with a lower alcohol to produce an iminoether, subjecting the product produced, after subjecting the iminoether to reaction with a reactive derivative of an organic acid, to hydrolysis and further eliminating the ester group of the carboxylic acid.

Process for preparing cephalosporanic acid derivatives

A process for preparing a cephalosporin ester which comprises subjecting an organic halide or an alcohol to reaction with a cephalosporin acid, a cephalosporin acid halide or a salt thereof in the presence of liquid sulfur dioxide.

Process for preparing cephalosporin esters in the presence of liquid

Compounds are provided having the general formula I: ##STR1## wherein X represents an hydroxyl group, an acetoxy group or a thiosulfuric acid residue. The formula I compounds are prepared from compounds of the general formula II: ##STR2## wherein R.sub.1 represents hydrogen, a lower alkanoyl group, an arylalkanoyl group, an alkoxycarbonyl group, a lower haloalkoxycarbonyl group, a substituted or unsubstituted aroyl group, a N-arylcarbamoyl group of a substituted or unsubstituted aryl group; R.sub.2 either represents hydrogen or, together with the ##STR3## group, represents a phthalimido group; and X represents an hydroxyl group, an acetoxy group or a thiosulfuric acid residue, or their metal salts or their salts with organic bases, by causing the culture of a cephalosporin C acylase-producing strain of a microorganism, especially a mold, fungus, or the secondary preparation therefrom, to act on the latter compounds II in the presence of an aqueous medium.

Process for the preparation of 7-amino-cephem compounds using mold fungi

A novel ester of 7-acylamido-3-methyl-cepham-4-carboxylic acid derivative and a process for the preparation thereof which comprises reacting penicillin sulfoxide ester with the metal halide, and a novel 7-acylamido-3-methyl-cepham-4-carboxylic acid derivative and a process for the preparation thereof which comprises reacting penicillin sulfoxide ester with the metal halide and decomposing the resultant in a reductive atmosphere.

Process for the preparation of

A cephalosporin compound represented by the formula (I) or (I') ##STR1## wherein R.sup.1 represents a phenyl group, a 2-thienyl group or a phenoxy group; R.sup.2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms which may be substituted with a phenyl group, an alkoxy group having 1 to 4 carbon atoms or a halogen atom, or a phenyl group which may be substituted with one or two groups selected from the group consisting of a halogen atom, a nitro group, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; R.sup.3 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may be substituted with a monoalkylamino group having 1 to 4 carbon atoms in the alkyl moiety thereof, a dialkylamino group having 1 to 4 carbon atoms in each alkyl moiety thereof, a halogen atom or a phenyl group which may be substituted with one to three groups selected from the group consisting of a halogen atom, a nitro group, an alkyl group having 1 to 4 carbon atoms and an alkoxy group having 1 to 4 carbon atoms; R.sup.4 represents an alkyl group having 1 to 4 carbon atoms; A has up to 15 carbon atoms and represents a straight or branched chain alkylene group, a straight or branched chain alkenylene group, a straight or branched chain alkadienylene group or a phenylene group, and n is 0 or 1; or the salt thereof; and a process for preparing the same.

Cephalosporin-type antibiotics and process for producing the same

As new semi-synthetic antibiotic derivative are provided N-methanesulfonic acid derivatives of 3',4'-dideoxykanamycin B which are less toxic than the parent antibiotic and have useful high antibacterial activity. They are produced by interacting 3',4'-dideoxykanamycin B, an aldehyde such as paraformaldehyde and sulfurous acid or an alkali metal sulfite reagent.

N-methanesulfonic acid derivatives of 3',4'-dideoxykanamycin B

A compound having the formula: ##EQU1## and a 7-amihocephalosporanic acid derivative having the formula: ##SPC1## Are reacted in a homogeneous aqueous solution of the reactants to prepare a reaction of the formula: ##SPC2## In the formulas, R may be H or other defined substituents such as carboxyl group; R.sub.1 is H, an alkyl of 1-4 carbons or other defined substitents; R.sub.2 is H or phenyl or when taken together with R.sub.1 form a defined cyclicradical; R.sub.3 is H or other defined substituents and M is an alkali metal cation, ammonium cation or H.

Process for N-acylation of 7 amino cephem compounds

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Tokyo, Japan

Shigeo Seki