Sumitomo Chemical Company, Limited

Shigeru Okano

Toshiaki Komatsu

Hisao Tobiki

Kozo Shimago

Yasuko Eda

Hiroshi Noguchi

Takenari Nakagome

Hirotada Yamada

Iwao Nakatsuka

Akio Izawa

Yoshio Suzuki

Hiroyuki Suzuki

Toshihiko Hibino

Hisao Akiyama

Yoichi Hara

Etsuro Sato

Yasuhiko Aoki

Toyozo Katsura

Yasushi Taira

A new method for the production of intermediates in the synthesis of an optically active biotin, which comprises reacting a dicarboxylic acid of the formula: ##SPC1## Or its reactive derivative with an optically active primary amine, reducing the resulting trione with a metal hydride, hydrolyzing the resultant amide-alcohol and treating the thus produced lactone with a thiolactonating agent to give a thiolactone of the formula: ##SPC2## , the said trione and amide-alcohol being respectively novel and representable by the formulae: ##SPC3##

Method for synthesis of optically active thiolactones

A penicillin of the formula: ##STR1## wherein ##STR2## is a six-membered heteroaromatic ring containing 1 or 2 nitrogen atoms as the hetero atom, Y is hydrogen, lower alkanoyl or lower alkoxycarbonyl, R.sub.1 and R.sub.2 are each hydrogen, lower alkyl, lower alkanoyl, benzoyl, lower alkylmercapto, hydroxyl, mercapto, hydroxy(lower)alkyl, halogen or cyano or R.sub.1 and R.sub.2 may link together to form a lower alkylene chain which may be substituted with an oxo group, and Z is phenyl, hydroxyphenyl, lower alkyl, cyclohexadienyl, thienyl or isothiazolyl, which is prepared by reacting a compound of the formula: ##STR3## wherein Z is as defined above or its derivative with a carboxylic acid of the formula: ##STR4## wherein ##STR5## and R.sub.2 are each as defined above or its reactive derivative, if necessary, followed by hydrolysis or acylation of the resulting product and/or elimination of any protective group and which is useful as an antimicrobial agent against various gram-positive and gram-negative bacteria including Pseudomonas.

Penicillins

Novel penicillins of the formula: ##STR1## wherein the ring A is a benzene ring or a 5 or 6-membered heteroaromatic ring containing one or two nitrogen atoms as the hetero atom, on which one or more of lower alkyl, lower alkoxy, lower alkylthio, lower haloalkyl, lower alkylenedioxy halogen, hydroxyl, nitro, free or protected amino, lower alkylamino, di(lower)alkylamino and lower alkanoylamino may be present, Z is a nitrogen atom or a methylene group, X is an oxygen atom or a sulfur atom, Y is a hydrogen atom, a lower alkoxycarbonyl group or a lower alkanoyl group, R.sub.1 is a free or protected hydroxyl group and R.sub.2 and R.sub.3 are each a hydrogen atom or a halogen atom, and their non-toxic pharmaceutically acceptable salts, and their preparation.

Novel penicillins and their preparation

Novel penicillins of the formula ##SPC1## Wherein ##EQU1## represents a substituted or unsubstituted benzene or nitrogen atom-containing heteroaromatic ring which may be substituted, ##EQU2## represents a pyridine, pyrazine or pyridazine ring, X represents an oxygen or sulfur atom, Y represents a hydrogen atom or a loer alkoxycarbonyl or lower alkanoyl group, and R.sub.1, R.sub.2 and R.sub.3 are each a hydrogen or halogen atom or a nitro, lower alkylamino, di(lower)alkylamino, aine, lower alkoxycarbonylamino, lower alkanoylamino, amino(lower)alkyl, lower alkyl, lower alkoxy, hydroxyl, sulfamoyl, trifluoromethyl, lower alkylthio or lower alkylsulfonyl group, excluding the cases where all of R.sub.1, R.sub.2 and R.sub.3 are hydrogen atoms and where R.sub.1 is a hydroxyl group and R.sub.2 and R.sub.3 are each a hydrogen or halogen atom, and their nontoxic, pharmaceutically acceptable salts, which can be prepared by reacting a carboxylic acid of the formula: ##EQU3## wherein ##EQU4## X and Y are each as defined above or its reactive derivative with a compound of the formula: ##SPC2## Wherein R.sub.1, R.sub.2 and R.sub.3 are each as defined above or its reactive derivative, and are ueful as antimicrobial agents against gram-positive and gram-negative bacteria including Pseudomonas.

Penicillins substituted with heterocyclic and substituted phenyl groups

Novel penicillins of the formula: ##SPC1## Wherein the ring A is a benzene ring or a 5 or 6-membered heteroaromatic ring containing one or two nitrogen atoms as the hetero atom, on which one or more of lower alkyl, lower alkoxy, lower alkylthio, lower haloalkyl, lower alkylenedioxy, halogen, hydroxyl, nitro, free or protected amino, lower alkylamino, di(lower)alkylamino and lower alkanoylamino may be present, Z is a nitrogen atom or a methylene group, X is an oxygen atom or a sulfur atom, Y is a hydrogen atom, a lower alkoxycarbonyl group or a lower alkanoyl group, R.sub.1 is a free or protected hydroxyl group and R.sub.2 and R.sub.3 are each a hydrogen atom or a halogen atom, and their non-toxic pharmaceutically acceptable salts, and their preparation.

Naphthyridine-3-carboxamido-benzylpenicillins and salts thereof

Novel benzothiazole derivatives of the formula ##SPC1## Wherein R.sub.1 and R.sub.2 are individually hydrogen, lower alkyl, nitro, halogen, optionally substituted amino, carboxyl, lower alkoxy-carbonyl or di-lower alkyl-carbamoyl; and R.sub.3 and R.sub.4 are individually hydrogen, lower alkyl or .alpha.-lower alkyl-benzyl or NR.sub.3 R.sub.4 is a saturated heterocyclic ring containing a nitrogen atom, and their salts. They are useful as antihypertensives.

Benzothiazole derivatives

A penicillin of the formula: ##SPC1## Wherein A is a substituted or unsubstituted condensed aromatic carbocyclic or heterocyclic ring, R is hydrogen or lower alkyl, X is oxygen or sulfur, Y is hydrogen, lower alkyl, lower alkanoyl or lower alkoxycarbonyl and Z is phenyl or thienyl which can be produced by reacting 6-aminopenicillanic acid or its ester with a carboxylic acid of the formula: ##SPC2## Wherein A, R, X, Y and Z are each as defined above or its reactive derivative. The said penicillin and its non-toxic salts have a broad antimicrobial spectrum against various gram-positive and gram-negative bacteria, and they exhibit characteristically a strong antimicrobial activity against Pseudomonas.

Penicillins substituted with heterocyclic groups

This invention relates to thiazole derivatives of the formula (I): ##EQU1## wherein R.sub.1 and R.sub.2 are each hydrogen, lower alkyl, cycloalkyl, optionally substituted aryl or optionally substituted heteroaromatic rings containing oxygen, sulfur, nitrogen or combinations thereof, and R.sub.3 and R.sub.4 are each hydrogen or lower alkyl and salts thereof. The thiazole derivatives of the formula (I) have excellent pharmacological properties such as .beta.-adrenergic receptor blocking effects and are valuable compounds exerting preventive or therapeutic effects on heart diseases, for example, arrhythmia, coronary heart disease, etc.

Thiazole derivatives

In the conversion of a hexahydrofuro[3,4-d]-imidazole-2,4-dione compound into the corresponding hexahydrothieno[3,4-d]imidazole-2,4-dione compound, an improved process which comprises reacting the starting hexahydrofuro[3,4-d]imidazole-2,4-dione compound with a dithiocarbamate.

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Kawanishi, Japan

Shigeru Okano