Teijin Limited

Sachio Ishimoto

Toshio Tanaka

Seizi Kurozumi

Takeshi Toru

Makiko Kobayashi

Shuzi Miura

Yoshinobu Hashimoto

Toru Takeshita

Sadakazu Matsubara

Yataro Ichikawa

Yasuhiko Masuho

Takeshi Hara

Yoshinori Kato

Koji Nakagawa

Hideki Tsuruta

Hisao Yamaguchi

Takeo Oba

Hiroyuki Kawashima

Katsuhiko Tomibe

Kimihiko Matsuzawa

Kazuhiko Itoh

Yasutaka Kayama

Masuo Morisaki

Nobuo Ikekawa

Toshiro Mori

Hitoshi Fujimori

Tamiko Sunami

Kazuo Satake

Tsuneo Watanabe

Kenji Ozawa

Shuji Miura

Novel 4H-pyrrolo[1,2-a][1,4]benzodiazepine derivatives of the formula ##STR1## wherein at least one of R.sub.1, R.sub.2 and R.sub.3 represent lower alkyl and the remainder hydrogen, R.sub.4 represents hydrogen or lower alkyl, ring A optionally contains at least one substituent selected from halogen, nitro and trifluoromethyl, and ring B optionally contains at least one substituent selected from halogen, nitro, trifluoromethyl, lower alkyl and lower alkoxy; and novel intermediates thereof expressed by the formula ##STR2## wherein Z represents protected amino. Compounds of formula (I) are prepared by subjecting compounds of formula (II) to protective group-elimination and cyclization. The compounds of formula (I) and acid addition salts thereof have useful anti-anxietic, sedative, anti-convulsant, muscle relaxant and hypnotic, and their toxicity is low.

Benzodiazepine derivatives and pharmaceutical compositions containing

1,3-Dicarbonyl compounds useful as medicines, agricultural chemicals, perfumes, and their intermediates are prepared by reacting a specific .alpha.,.beta.-unsaturated carbonyl compound with a specific organic copper lithium compound in the presence of an aprotic inert organic solvent, and then reacting the reaction product with an organic carboxylic acid halide or anhydride. In particular, novel 2-acyl-3-substituted cyclopentan-1-ones and 2-acyl-3-substituted cyclohexan-1-ones having important physiological activities are provided.

1,3-Dicarbonyl compounds

Novel substituted hydrazide derivatives of 7-(substituted)amino-3-methylene-cepham-4-carboxylic acids expressed by the formula ##STR1## wherein R.sub.1 represents alkyl containing at least 3 carbon atoms, cycloalkyl, or optionally substituted aryl, and one of R.sub.2 and R.sub.3 represents hydrogen with the other being hydrogen or the same as R.sub.1 ; or R.sub.1 and R.sub.2 form a heterocyclic ring optionally through a hetero atom together with the attached nitrogen and R.sub.3 represents hydrogen atom; and Z.sub.1 represents amino or protected amino; and acid addition salts thereof, which are useful as intermediates for synthesizing cephalosporin antibiotics. These compounds can be prepared in high yields from the corresponding substituted hydrazide derivatives of 6-substituted amino-1-oxide-2, 2-dimethyl-penam-3-carboxylic acids, which are readily available at low costs, by heating them in the presence of a thermal rearrangement promotor such as organic sulfonic acids and optionally in the further presence of a tertiary nitrogen-containing cyclic compound, followed if desired by splitting off the amino-protecting group and converting the product to acid addition salts.

3-Methylene cephalosporanic acid derivatives and process for preparation

Novel optically active compounds of 4-protected hydroxy-cyclopent-2-en-1-ones of the formula ##STR1## wherein R is a splittable protective group for an alcoholic hydroxyl group, and a process for preparing the 4-protected hydroxycyclopent-2-en-1-ones by oxidizing monohydroxy-protected derivatives of cyclopent-1-ene-3,5-diol expressed by the following formula ##STR2## wherein R is the same as defined above. Optically active 4-hydroxycyclopent-2-en-1-one which is an optically active isomer of the compound of formula (2); or optically active cyclopent-1-en-3,5-diol (R-isomer) and a novel diacyl derivative of the diol, a novel monoacylmonosilyl-derivative of the diol and a novel monoacylmonotetrahydropyranol-derivative of the diol, which are intermediates for the protective derivative of formula (1). Processes are also provided for preparing the protective derivatives of formula (1) by converting these intermediates by esterification, hydrolysis, enzymatic processes, etc. The optically active compounds of formula (2) are useful as precursors for the preparation of prostaglandin or its analogues.

Process for the preparation of 4-hydroxycyclopent-2-en-1-one derivatives

Novel immunoglobulin derivatives which are characterized in that in which the interchain disulfide bonds of immunoglobulin are predominantly cleaved, on the average 3 to 5 of the interchain disulfide bonds or the inter- and intra-chain disulfide bonds being cleaved, and so produced sulfur atoms (S-) are S-sulfonated (--S-SO.sub.3). The above immunoglobulin derivatives are prepared by reacting native immunoglobulin with A. a compound capable of forming tetrathionate ion, and B. a compound capable of forming in water, sulfite ion whereby cleaving on the average 3 to 5 inter-chain disulfide bonds, or inter- and intra-chain disulfide bonds, of the native immunoglobulin, and S-sulfonating (S-SO.sub.3) the so formed sulfur atoms. This invention also provides a water-soluble composition for injection containing said immunoglobulin derivative having the titre of anti-diphtheria of at least 1.0 I.U./ml at its concentration of 10.0% by weight, and a pharmaceutically-acceptable solubilizing agent for said immunoglobulin derivative.

Novel immunoglobulin derivatives and process for the preparation thereof

A process for preparing cyclopent-2-en-1-one derivatives of the formula ##STR1## wherein R.sub.1 is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group, and

Process for preparing cyclopent-2-en-1-one derivatives

Novel 1.alpha., 24-dihydroxycholecalciferol and derivatives thereof which are useful with reduced side-effects for the treatment of abnormal metabolism of calcium and phosphorus caused by liver failure, renal failure, gastrointestinal tract failure and parathyroid failure, and related bone diseases. Preparation of the novel 1.alpha., 24-dihydroxycholecalciferol and their derivatives starts from 1.alpha., 24-dihydroxycholesterol prepared by reacting 1.alpha., 2.alpha.-epoxy-24-keto-cholesta-4,6-dien-3-one with an alkali metal and a proton donor in the presence of liquid ammonia or a liquid amine. Reaction of the 1.alpha., 24-dihydroxycholesterol with an allylic brominating agent, followed by contacting with a dehydrobrominating agent, affords 1.alpha.,3.beta., 24-trihydroxycholesta-5,7-diene derivative, which can then be converted to 1.alpha., 24-dihydroxycholocalciferol by ultraviolet irradiation in a organic solvent, followed by isomerization. Processes are also provided for separating 1.alpha., 24-dihydroxycholesterol into an (S)-epimer and an (R)-epimer, and also for separating at least one of 1.alpha., 3.beta., 24(S)-and 1.alpha., 3.beta., 24(R)-trihydroxycholesta-5,7-dienes from trihydroxycholesta-4,6-diene.

Novel 1.alpha.,24-dihydroxycholecalciferol compositions, novel

2-Acyl-3-substituted cyclopentan-1-ones and process for their preparation

New optically active cyclopentene-diol and the mono- or diacyl esters thereof and a process for converting a diacyl ester of cyclopent-1-en-3,5-diol to its monoacyl ester and/or its diol which comprises subjecting a diacyl ester of cyclopent-1-en-3,5-diol containing at least one of the optically active or inactive diacyl ester of trans-cyclopent-1-en-3,5-diol (trans-isomer) and diacyl esters of cis-cyclopent-1-en-3,5-diol (cis-isomer), to the action of a microorganism or enzyme having at least a selectivity in its rates of hydrolyzing the acyloxy group (R) configuration and the acyloxy group (S) configuration of said diacyl ester. These new compounds are valuable as starting materials for the preparation of prostaglandin or its analogues.

New cyclopentene-diols and new acyl esters thereof and process for their

A process for the preparation of 1,4-diacetoxycyclopent-2-ene, which comprises contacting a solution of 1,4-dibromocyclopent-2-ene in an inert organic solvent which is slightly soluble or insoluble in water, with an aqueous solution or suspension of at least one metal salt of acetic acid which is at least partially water-soluble, in the presence of a cationic surface-active compound.

Process for the preparation of 1,4-diacetoxycyclopent-2-ene

A process for the preparation of desmosterol of which the hydroxyl group at the 3-position is protected, or bis-form derivatives thereof in high purity and with high yields, which comprises reacting 24-hydroxycholesterol of which the hydroxyl group at the 3-position is protected, or bis-form derivatives thereof, with

Process for the preparation of desmosterol derivatives

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Tokyo, Japan

Sachio Ishimoto