Nippon Kayaku Kabushiki Kaisha

Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Hiroshi Yoshikawa

Hamao Umezawa

Tomio Takeuchi

Shinichi Kondo

Hitoshi Sato

Tomohisa Takita

Yoshinobu Miyazawa

Yoshio Nishimura

Kouichi Ohkawa

Wataru Tanaka

Noriko Tomiyoshi

Seiichi Saito

Masayuki Kitagawa

Hiroo Hoshino

Katsuhiko Kurabayashi

Yukihiro Fusauchi

Haruo Machida

Junichi Seki

A protected 4'-demethyl-4-epipodophyllotoxin is reacted with a protected glucose derivative in a non-halogen type organic solvent in a 0.1-7-fold parts by volume based on 1 part by weight of the protected 4'-demethyl-4-epipodophyllotoxin to give an etoposide derivative of formula (3) which is protected at its functional groups: ##STR1## wherein each of R.sub.1 and R.sub.2 each is a protective group for hydroxy, if necessary, followed by removal of these protective groups. By use of the non-halogen type organic solvent in lieu of any harmful halogen type solvent, formation of undesirable by-products can be minimized so that the etoposides can be obtained in a high yield and high purity.

Process for producing etoposide

An etoposide phosphate represented by the formula ##STR1## is prepared by blocking the hydroxyl groups of the saccharide moiety of etoposide with halogenoacetyl groups, thereafter phosphorylating the 4'-position, and removing the halogenoacetyl groups from the obtained phosphate in the presence of an amine. This process can give the objective etoposide phosphate in a higher yield than that of the prior art to enable the industrial mass-production thereof.

Process for the preparation of etoposide phosphate and intermediate

An etoposide phosphate represented by the formula (1): ##STR1## is prepared by blocking the hydroxyl groups of the saccharide moiety of etoposide with halogenoacetyl groups, thereafter phosphorylating the 4'-position, and removing the halogenoacetyl groups from the obtained phosphate in the presence of an amine. This process can give the objective etoposide phosphate in a higher yield than that of the prior art to enable the industrial mass-production thereof.

Etoposide phosphate and preparative intermediates

Oxetanocin derivatives represented by formula: ##STR1## wherein X represents H or ##STR2## or a pharmacologically acceptable salt thereof exhibit an anti-viral activity. Anti-viral compositions comprising the oxetanocin derivatives or their pharmacologically acceptable salts as the effective ingredient are also provided.

Oxetanocin derivatives and their salts as well as use thereof

This invention relates to a novel 4'-demethyl-4-epipodophylltoxin derivative of the formula: ##STR1## (wherein R.sub.1 is a lower alkyl group; X.sub.1 and X.sub.2 are each a hydroxyl group or an amino group substituted by one or two lower alkyls, provided that either one of X.sub.1 and X.sub.2 is an amino group substituted by one or two lower alkyls and the other is a hydroxyl group) and salts thereof.

4'-demethyl-4-epipodophyllotoxin derivative

This invention relates to novel 4'-demethyl-4-epipodophyllotoxin derivatives represented by the general formula (I), and salts thereof: ##STR1## wherein R is a lower alkyl group, and X.sub.1 and X.sub.2 are independently a hydroxyl group or an amino group, the one being an amino group and the other being a hydroxyl group. These novel derivatives have a high carcinostatic activity and a relatively high water solubility and hence are expected to be useful as carcinostatics.

Derivatives of 4'-demethyl-4-epipodophyllotoxin

Disclosed herein is a process for producing 2-chloro-6-nitrobenzonitrile by making reaction of 2,3-dichloronitrobenzene and an alkali cyanide in an aprotic solvent or in a basic solvent in the presence of cuprous chloride or in the presence of cuprous chloride and a cupric salt.

Process for producing 2-chloro-6-nitrobenzonitrile

A process for the production of 2-chlorobenzonitrile derivatives represented by the general formula (I): ##STR1## (wherein n is a number of 1 or 2) characterized by reacting a compound of the general formula (II): ##STR2## (wherein Cl.sub.n is as defined above) with lithium chloride or a mixture of lithium chloride and anhydrous aluminum chloride or with lithium aluminum chloride in an aprotic solvent.

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Fujioka, Japan

Hiroshi Yoshikawa