Eisai Company, Limited

Eisai Chemical Co., Ltd.

Kimio Hamamura

Shizumasa Kijima

Chiaki Seki

Masayuki Konishi

Youji Yamagishi

Isao Yamatsu

Norio Minami

Yuichi Inai

Tetsuo Iwama

Toshiji Igarashi

Noriyasu Hirose

Yoshikage Nakajima

Takashi Banba

Kiiti Ema

Yuithi Inai

Tetsuya Nakamura

Takaharu Nakamura

Nozomu Koyanagi

Kozo Akasaka

Yoshio Urawa

Hiroshi Shionoya

Haruyoshi Arai

Hidetoshi Kawashima

Keizo Takayanagi

Eiichi Morita

Yoshihiko Hisatake

Yasuhide Tanaka

Yukio Morita

Noritoshi Sano

Yukio Narabe

Homare Shinohara

Hirofumi Kuroda

Hirosaburo Ejiri

Yuko Miyauchi

Yuuichi Inai

Masato Kodama

Isao Yamatu

An industrially excellent, novel process for producing cephem compounds which are useful as medicines, particularly, antibiotics and represented by the following formula (III): ##STR1## wherein R.sup.1 means either group represented by the following formula: ##STR2## R.sup.2 denotes a carboxyl group or a carboxyl anion, and R.sup.3 stands for a lower alkyl group, a halogen atom, a lower alkyl group substituted by an aliphatic acyloxy group having 1-6 carbon atoms, or any one of the groups represented by the following formulae: ##STR3## which comprises reacting in water a 3-cephem-4-carboxylate represented by the following formula (I): ##STR4## or a salt thereof with an acid chloride represented by the formula (II), R.sup.1 COCl.

Process for producing cephem compounds in an aqueous medium

A hydroquinone derivative (I) represented by the following formula: ##STR1## wherein R.sup.1 is a hydrogen atom, acetyl group or benzoyl group, such hydroquinone derivative being useful as an intermediate for chroman derivatives useful as a blood sugar-lowering agent.

Butenyl hydroquinone derivatives

Disclosed herein are a quinone derivative represented by the following formula: ##STR1## wherein R.sup.1 and R.sup.2 are identical with or different from each other and mean individually a lower alkyl or lower alkoxy group, or may form an aromatic ring together, R.sup.3 denotes a lower alkyl group, n stands for 0 or an integer of 1-9, and a linkage --- is a single or double bond, such as a vitamin K derivative or coenzyme derivative; and a process for the preparation of the quinone derivative at a high yield without forming any geometric isomer; as well as a 1,4,4.sub.a,8.sub.a -tetrahydro-4.sub.a .alpha.-alkenyl-1.alpha.,4.alpha.-methanonaphthalene-5,8-dione derivative which is useful as an intermediate for the preparation of the quinone derivative.

Tetrahydro-alkenyl-methanonaphthalene-5,8-dione derivatives

Disclosed herein are a quinone derivative represented by the following formula: ##STR1## wherein R.sup.1 and R.sup.2 are identical with or different from each other and mean individually a lower alkyl or lower alkoxy group, or may form an aromatic ring together, R.sup.3 denotes a lower alkyl group, n stands for 0 or an integer of 1-9, and a linkage--is a single or double bond, such as a vitamin K derivative or coenzyme Q derivative; and a process for the preparation of the quinone derivative at a high yield without forming any geometric isomer; as well as a 1,4,4.sub.a,8.sub.a -tetrahydro-4.sub.a .alpha.-alkenyl-1.alpha.,4.alpha.-methanonaphthalene-5,8-dione derivative which is useful as an intermediate for the preparation of the quinone derivative.

Process for the preparation of quinone derivative

The present invention relates to intermediates useful for the preparation of vitamin K derivatives.

1,4,4.sub.a 5,8,9.sub.a

A process for the industrial preparation of the quinone derivative represented by the following general formula: ##STR1## which is an intermediate for chroman derivatives useful as a blood sugar lowering agent, and novel intermediates, encompasses the following: (1) Oxidation of the corresponding hydroquinone derivative, and (2) Hydrolysis of the corresponding acyl hydroquinone derivative with a Claisen alkali, followed by the oxidation of resulting hydrolyzate.

Oxidative process for the preparation of allyl quinone derivatives

Disclosed herein are a quinone derivative represented by the following formula: ##STR1## wherein E.sup.1 and E.sup.2 are identical with or different from each other and mean individually a lower alkyl or lower alkoxy group, or may form an aromatic ring together, E.sup.3 denotes a lower alkyl group, n stands for 0 or an integer of 1-9, and a linkage ------ is a single or double bond, such as a vitamin K derivative or coenzyme Q derivative; and a process for the preparation of the quinone derivative at a high yield without forming any geometric isomer; as well as a 1,4,4.sub.a,8.sub.a -tetrahydro-4.sub.a .alpha.-alkenyl-1.alpha.,4.alpha.-methanonaphthalene-5,8-dione derivative which is useful as an intermediate for the preparation of the quinone derivative.

Process for the preparation of a quinone derivative

Disclosed herein are a naphthoquinone derivative represented by the following formula: ##STR1## wherein R.sup.1 means a hydrogen atom or methyl group, R.sup.2 is a hydrogen atom or methyl group, n stands for 0 or an integer of 1-9, and a linkage is a single bond or double bond with the proviso that if n is an integer of 2-9, the linkages may be identical with or different optionally from each other, such as a vitamin K derivative; and a process for producing the naphthoquinone derivative at a high yield without forming any geometric isomer; as well as 1,4,4.sub.a,5,8,9.sub.a -hexahydro-4.sub.a .alpha.-alkenyl-1.alpha.,4.alpha.-methanoanthraquinone derivatives and 1,4,4.sub.a,5,8,9.sub.a -hexahydro-1.alpha.,4.alpha.-methanoanthraquinone derivatives which are useful as intermediates for the preparation of the naphthoquinone derivatives.

Preparation process of naphthoquinone derivative and intermediate for

A terpene derivative represented by the general formula (I): ##STR1## wherein R.sup.1 represents a lower alkyl group; R.sup.2 represents an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an arylalkyl group or a heteroaryl group; n is 0 or 1 or 2; and the symbol '  ' represents a single or double bond with the proviso that both of the linkages adjacent to each other are not simultaneously single bonds or double bonds which are useful for the preparation of drug, food, perfume and so on, and a process for preparing thereof.

Terpene derivatives and process for preparing the same

2,3,5-trimethyl-benzoquinone is produced by oxidizing 2,3,6-trimethyl-phenol in the presence of a catalyst of cupric chloride and lithium chloride in a solvent mixture of an aromatic hydrocarbon and a lower aliphatic alcohol having 1 to 4 carbon atoms.

Process for preparing 2,3,5-trimethylbenzoquinone

The novel vitamin E derivative provides an excellent antihyperlipemic effect and is defined by the formula (I): ##STR1## wherein R represents a nicotinoyl group; and m is an integer of from 2 to 5 while n is an integer of from 3 to 6, provided that n is larger than m.

Novel vitamin E derivatives and process for the production thereof

Optically active alpha-tocopherol is synthesized by a multi-step process using phytol as a starting material. The process does not require an optical resolution step.

Synthesis of optically active d-alpha tocopherol

2-METHYL-3-PRENYL-4,5,6-TRIMETHOXYPHENOL OF THE FORMULA: ##STR1## wherein R represents a group of the formula: ##STR2## WHEREIN N IS AN INTEGER OF 0 TO 9 AND A and B represent hydrogen atom or A--B may form a bond, Is prepared by reacting 6-methyl-2,3,4-trimethoxyphenol with a prenol or isoprenol substituted by the group R as defined above in the presence of a complex catalyst comprising Lewis acid and a silica-alumina compound.

Process for preparing 2-methyl-3-prenyl-4,5,6-trimethoxyphenol

Novel 5-fluorouracil derivatives of the general formula: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 each represent hydrogen atom or methyl group, and R.sub.4 represents a straight or branched alkyl or alkenyl group, which has low toxicity and improved antitumor activity, and novel antitumor preparations containing the said 5-fluorouracil derivative.

5-Fluorouracil derivatives and antitumor preparations containing the same

A polyprenyl carboxylic acid compound represented by the following general formula: ##STR1## wherein R stands for a hydrogen atom or an alkyl, alkenyl, cycloalkyl or aryl group, and n is an integer of 6 to 11. This compound is effective to treat hypertension of warm blooded animals.

Growing community of inventors

Chiba, Japan

Kimio Hamamura