Mitsui Petrochemical Industries, Ltd.

Naoya Sakamoto

Noriaki Kihara

Hiroaki Tan

Michio Tanaka

Toshihiro Takai

Masayasu Ishibashi

Katsuo Taniguchi

Kazunori Takahata

Masahiro Kondo

Yoshito Kurano

Takeshi Ishitoku

Eiichiro Hata

Hajime Ooyoshi

Eiichirou Hata

The present invention relates to a process for the preparation, from e.g. anhydrovinblastine, of binary indole alkaloids effective as an anti-cancer drug, such as vinblastine, leurosidine, etc., wherein a trivalent iron source and hydride source are added in the presence of oxygen, thereby increasing a yield of an object compound. The yield of an object compound is improved still more by further addition, to the reaction system, of an oxalic acid ion source, malonic acid ion source, inorganic anion source, amino acid, etc.

Process for the preparation of binary indole alkaloids

In a method of producing a keto acid having the general formula ##STR1## wherein R.sup.1 and R.sup.2 independently represent an alkyl of 1-6 carbons or a cycloalkyl of 4-8 carbons, by reacting an m-aminophenol having the general formula ##STR2## wherein R.sup.1 and R.sup.2 are the same as above, with phthalic anhydride, in an organic solvent, the improvement comprising effecting the reaction in an amount of the organic solvent which is insufficient to dissolve the keto acid produced in the reaction, so that at least a portion of the resultant keto acid crystallizes out of the solvent and allowing the reaction to proceed in a heterogeneous system.

Method of producing keto acids

This invention concerns a method for the production of dimeric alkaloids, characterized by reacting of catharanthine with vindoline in the presence of Fe.sup.3+ and (1) removing or inactivating the Fe.sup.3+ and allowing the reaction product to react with a reducing agent or (2) allowing presence of oxygen and a dicarboxylic acid or a derivative thereof in the reaction system and allowing the reaction product to react with a hydride source. In accordance with this invention, such dimeric alkaloid as vinblastine, leurosidin, and 3',4'-anhydrovinblastine which are useful as antineoplastic drugs can be produced in high yields.

Method for production of dimeric alkaloids

Process for producting alkyl group-substituted aromatic hydrocarbons

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Yamaguchi, Japan

Naoya Sakamoto