Teijin Limited

Hideki Tsuruta

Yataro Ichikawa

Toru Takeshita

Kenji Ishimaru

Yoshiyuki Yamanaka

Osamu Nishikawa

Mamoru Yamamoto

Kenichi Kato

Teizo Yamaji

Yoshinori Kato

Koji Nakagawa

Sachio Ishimoto

Toshiyuki Hiramatsu

Itaru Yamamoto

Hisao Yamaguchi

Eishin Yoshisato

Takeo Oba

Nobuo Suzuki

Jun-ichi Oshida

Kenji Ozawa

The present invention relates to novel vitamin D.sub.3 derivatives which have a carboxyl group or its ester group at the 22-position, processes for the preparation thereof, and antigens, which comprise said vitamin D.sub.3 derivative and an immunogenic carrier material, to be used for the preparation of antibodies for enzymeimmunoassay or radioimmunoassay and antibodies obtained therefrom. The determination of such activated vitamin D.sub.3 compounds as 25-hydroxy vitamin D.sub.3, 24, 25-dihydroxy vitamin D.sub.3, etc. can be made satisfactorily according to the present invention.

Vitamin D.sub.3 derivatives, process for preparation thereof, and

The present invention relates to a novel process for the preparation of active-type vitamin D.sub.3 compounds and their intermediates. In accordance with the present invention, a large amount of an active-type vitamin D.sub.3 compounds, for example 1.alpha.-hydroxycholecalciferol, 1.alpha.,25-dihydroxycholecalciferol and the like, is efficiently prepared with high industrial advantages by a novel processes, which comprises (i) reacting hydroxycholesta-5-enes having the hydroxyl groups protected with lower alkoxycarbonyl group as a starting material with allylic brominating agent and dehydrobrominating agent to prepare the corresponding hydroxycholesta-5,7-dienes, (ii) exposing the hydroxycholesta-5,7-dienes to ultraviolet irradiation or to a combination of the irradiation with thermal isomerization to obtain a mixture of the unreacted hydroxycholesta-5,7-dienes and previtamin D.sub.3 compounds or a mixture of the unreacted hydroxycholesta-5,7-dienes and the protected active-type vitamin D.sub.3 compounds, (iii) separating the mixture into the unreacted hydroxycholesta-5,7-dienes and previtamin D.sub.3 compounds or the protected active-type vitamin D.sub.3 compounds, (iv) recycling the unreacted hydroxycholesta-5,7-dienes as reuse and (v) thermally isomerizing the remaining compounds and/or splitting off the protective groups. The process for the preparation of active-type vitamin D.sub.3 compounds, in the present invention, is of very high industrial value, capable of carrying out by simple operation and adaptable to large scale commercial production.

Process for the preparation of active-type vitamin D.sub.3 compounds

A process for producing a steroid compound having an oxo group in the side chain, which comprises condensing an acid halide having a steroid skeleton with an organozinc compound at the halocarbonyl group of the acid halide in an inert organic medium in the presence of a catalytic amount of an ether capable of forming a complex with the organozinc compound, and if desired, hydrolyzing the product. The process produces the steroid compound at a high yield, and often at an almost quantitative yield. The steroid compound is an important intermediate for the production of vitamin D.sub.3 analogs such as active forms of vitamin D.sub.3. In one preferred embodiment, an industrially advantageous process from the standpoint of operation is provided.

Process for producing steroid compounds having an oxo group in the side

This invention relates to novel 25-hydroxy-24-oxocholestane derivatives and a process for preparing them. The novel 25-hydroxy-24-oxocholestane derivatives of this invention can easily be converted to 24,25-dihydroxycholecalciferol or 1.alpha.,24,25-trihydroxycholecalciferol which is known as useful for medicine controlling the calcium metabolism of warm-blooded animals. Moreover, 25-hydroxy-24-oxocholestane derivatives can be converted to novel 25-hydroxy-24-oxocholecalciferol expressed by the following formula ##STR1## and novel 1.alpha.,25-dihydroxy-24-oxocholecalciferol of the formula ##STR2## which are useful for medicine. The new 25-hydroxy-24-oxocholestane derivatives in the present invention are very useful as the intermediates for the synthesis of a variety of active vitamin D.sub.3.

25-Hydroxy-24-oxocholestane derivatives and preparation thereof

An inclusion compound comprising meta-cyclophane of the formula ##STR1## and at least one benzene derivative included therein. And a process for separating an isomer containing a substituent at least at the 1- and 4-positions from a mixture containing isomers of a benzene derivative, which comprises contacting the meta-cyclophane with the mixture containing isomers of a benzene derivative thereby to form an inclusion compound in which an isomer containing a substituent at least at the 1- and 4-positions is included in the meta-cyclophane, then separating the inclusion compound from the mixture, and thereafter separating the isomer from the inclusion compound.

Inclusion compounds, process for preparation thereof, and process for

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

An inclusion complex compound comprising (a) meta-cyclophane and (b) a trans-terpenoid of the formula ##STR1## wherein n is an integer of 1 to 9; A.sub.1 and A.sub.2 each represent (1) a hydrogen atom, (2) a halogen atom, (3) an inorganic group containing an oxygen, nitrogen or sulfur atom, (4) an organic group containing 1 to 5 carbon atoms, or (5) an organic group containing an oxygen, nitrogen or sulfur atom and 1 to 5 carbon atoms; and C* is the carbon atom of a carbonyl or methylene group, Included by the meta-cyclophane. This inclusion complex compound can be prepared by contacting the meta-cyclophane with a mixture containing the trans-terpenoid. A trans-terpenoid can be separated from a mixture containing it by utilizing an inclusion complex compound of it with meta-cyclophane.

Inclusion complex compound, process for its production, and method for

A process for recovering purified 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadiene-1-one by distilling crude 4-hydroxy-,2,4,6-trimethyl-2,5-cyclohexadien-1-one. Preferably, the distillation is performed at a temperature of 40.degree. to 250.degree.C. using crude 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadien-1-one having a pH of 4 to 11.5. Thus, 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadien-1-one of high purity and reduced coloration can be recovered at a high recovery ratio.

Process for recovering purified

A process for preparing 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadiene-1-one comprising reacting 2,4,6-trimethyl phenol with molecular oxygen or a molecular oxygen-containing gas. The product (also called mesitylquinol) is an intermediate useful as a raw material for the synthesis of a variety of industrial chemicals such as a drugs, dyestuffs, and pigments.

Novel process for preparation of

This invention is directed to a process for preparing trimethylhydroquinone (TMHQ) by heating 4-hydroxy-2,4,6-trimethyl-2,5-cyclohexadiene-1-one (HTCD) in a nonacidic liquid medium consisting of either methanol or an aqueous medium, preferably in the presence of a basic substance, at a temperature of at least 100.degree.C., and preferably 150.degree.-300.degree.C. Thus, according to this invention, TMHQ of high purity and small coloration can be prepared from HTCD in good yield, for example, as high as 85 - 98%.

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Iwakuni, Japan

Hideki Tsuruta