Shionogi Company Limited

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Wataru Nagata

Teruji Tsuji

Yoshio Hamashima

Mitsuru Yoshioka

Masayuki Narisada

Ikuo Kikkawa

Tsutomu Aoki

Shoichiro Uyeo

Yasuhiro Nishitani

Hiroshi Tanida

Taichiro Komeno

Uyeo Shoichiro

Susumu Kamata

Hiromu Matsumura

Toshiro Konoike

Hiroshi Onoue

Hikaru Itani

Hiromi Takahashi

Sadao Hayashi

William H Lunn

Nobuhiro Haga

Hiroshi Itazaki

Tadatoshi Kubota

Yuji Sendo

Takeaki Matsui

Kanji Tokuyama

Hisao Sato

Mamoru Tanaka

Takashi Maeda

Shoichi Hirai

Takahiro Kataoka

Yoshio Hahashima

Sadao Yamamoto

Kyo Okada

Kyoto Okada

Matsumura Hiromu

An antibacterial cephalosporin hydroxamic acid derivative represented by the following formula (I), processes for its preparation, compositions containing the same as an active ingredient, and a method for killing bacteria by contacting with said compound. ##STR1## (wherein, R is acyl; R.sup.1 is hydrogen or methoxy; R.sup.2 is alkylene; R.sup.3 is hydrogen, aliphatic group or a hydroxy-protecting group; R.sup.4 is hydrogen or amino-protecting group; R.sup.5 is hydrogen, light metal atom or carboxy-protecting group; and X is oxygen, sulfur, or sulfinyl).

1-oxadethia cephalosporin hydroxamic acid derivatives

Cephalosporin hydroxamic acids

Highly selective and high yield process for producing antitumor agent 1-phthalidyl-5-fluorouracil derivatives of formula (I) which comprises reacting a phthalidyl compound (II) with an amine (III) to yield the quaternary ammonium salts (IV), and reacting the latter with 5-fluorouracil. ##STR1## [wherein X is leaving group; ##STR2## is triethylamine, N-methylmorpholine, N-ethylmorpholine, and the like; R.sup.4 and R.sup.5 each is hydrogen, trialkylsilyloxy, alkoxy, nitro, cyano, carboxy, or alkoxycarbonyl].

Production of 1-phthalidyl-5-fluorouracil derivatives

Intermediates for preparaing an antibacterial 1-dethia-1-oxacephalosporins which are represented by the following formula: ##STR1## wherein R is a monovalent group (minus the carbonyl) from an acyl derived from a carboxylic or carbonic acid;

1-oxadethiacepham compounds

Intermediates of the following formula are useful for the synthesis of 1-oxacephalosporins. Their preparation from penicillins and the transformation process to make 1-oxacephalosporins are disclosed. The compounds are of the formula: ##STR1## wherein A is amino or a selected acylamino;

Azetidinone intermediates for cephalosporin analogs

A novel chemical, fluorochlorocyclopropane (I) of the following formula: ##STR1## is prepared by the addition of fluorochlorocarbene to the corresponding olefin (II) of the following formula:

Fluorocyclopropanes

5-Mercapto-1H-tetrazole-1-alkanohydroxamic acid, its salts and its esters having the following formula: ##STR1## wherein A is an alkylene group;

Mercaptotetrazolylalkanohydroxamic acids, salts and ester thereof

Useful intermediates, 7.alpha.-acylamino-3-(oxo or exomethylene)-1-dethia-1-oxacepham-4.alpha.-carboxylates, are produced by the intramolecular carbenoid insertion of a 2-diazo-3-(oxo or exomethylene)-4-(3.alpha.-acylamino-2-oxoazetidin-4.beta.-yl)oxybutyrate prepared in several steps from the corresponding oxazolinoazetidinone and diketone.

Production of 1-oxacephams and intermediates

Intermediates for preparing an antibacterial 1-dethia-1-oxacephalosporins which are represented by the following formula: ##STR1## wherein R is a monovalent group (minus the carbonyl) from an acyl derived from a carboxylic or carbonic acid;

1-Oxadethiacepham compounds

A compound of the formula: ##STR1## wherein u represents hydrogen, carboxamido, N-hydroxycarboxamido, carboxy, azido, an aryl, an acylamino, a protected carboxy or an N-alkoxycarboxamido, or, together with v, can represent --S-- or --CH.sub.2 S--; v represents hydrogen, halogen, cyano or an alkylthio, or, together with u, can represent --S-- or --CH.sub.2 S--, or, together with w, can represent --(CH.sub.2).sub.3 CO--; w represents hydrogen, carboamoyl, cyano, carboxy, an N-alkylcarbamoyl, an alkyl, an aryl, a protected carboxy or a heterocycle, or, together with v, can represents --(CH.sub.2).sub.3 CO--; x represents halogen, trifluoromethyl, an alkylthio or an arylthio; y represents hydrogen, a light metal or a carboxylic acid protecting group; and z represents an acyloxy or a heterocycle-thio, each of the above radicals represented by the symbols u, v, w, x, y and z being optionally substituted by halogen or a carbon-, nitrogen-, oxygen- or sulfur-containing functional group, a process for preparing the compound, a pharmaceutical composition containing the compound, and a therapeutical use of the compound. A compound of the formula: ##STR2## wherein u, v, w and x are as defined above, useful as a starting compound for preparing the compound (I) is also provided.

Vinylthioacetamido oxacephalosporin derivatives

A phosphine sulfide derivative is chlorinated and hydrolyzed with little pollution problem to give the corresponding phosphine oxide derivative.

Process for preparing phosphine oxides

By heating an N-(2-hydroxyethyl)dithiocarbamate ester protected at its hydroxy group as an ether in the presence of an azide, the corresponding 1-(protected hydroxyethyl)-1H-tetrazole-5-thiol is obtained, and then, if required, deprotecting the etheric protection to give an industrially useful chemical, 1-(2-hydroxyethyl)-1H-tetrazole-5-thiol.

Synthesis of hydroxyethyltetrazolethiol and etherified intermediates

Intermediates for preparing an antibacterial 1-dethia-1-oxa-cephalosporins which are represented by the following formula: ##STR1## wherein R is a monovalent group (minus the carbonyl) from an acyl derived from a carboxylic or carbonic acid;

A process for preparing 3.beta.-amino-4.beta.-substituted-2-azetidinones, which comprises condensing a 3.alpha.-amino-4.beta.-substituted-2-azetidinone with a trihalogenoacetaldehyde or the reactive derivative thereof to give a 3.alpha.-(2,2,2-trihalogenoethylidene)amino-4.beta.-substituted-2-azetidin ones, treating the latter with a base to give a 3-(2,2-dihalogenovinyl)imino-4.beta.-substituted-2-azetidinone, reducing the latter with a metal hydride to give a 3.beta.-(2-halogenovinyl)amino-4.beta.-substituted-2-azetidinone, and hydrolyzing the latter to give the objective compound.

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Nishinomiya, Japan

Wataru Nagata