公开(公告)号：JPH0341081A

公开(公告)日：1991-02-21

申请号：JP17564289

申请日：1989-07-10

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  TAN HIROAKI ,  HATA EIICHIRO ,  KIHARA NORIAKI

IPC: C07D519/00 ,  C07D519/04

Abstract: PURPOSE:To produce the subject compound convertible to vinblastine useful as a carcinostatic agent in high yield on an industrial scale at a low cost by coupling catharanthine, etc., and a specific compound such as vindoline in the presence of trivalent, iron and phenanthroline, etc. CONSTITUTION:The objective compound of formula III can be produced by coupling (A) a compound of formula I (R1 to R4 are H or lower alkyl; R1 and R3 or R2 and R4 may together form epoxy or double bond; R5 is H or lower alkyl; R6 is H, lower alkyl or lower alkoxy) (e.g. catharanthine or dihydrocatharanthine) and (B) a compound of formula II (R1' is lower alkoxy; R2' is H, lower alkyl or formyl; R3' is lower alkoxycarbonyl or amido; R4' is alcohol residue or lower alkylcarboxy) (e.g. vindoline or N-formylvindoline) in the presence of (C) a medium comprising trivalent iron and a 1,10- phenanthroline (derivative).

公开(公告)号：JPH02231491A

公开(公告)日：1990-09-13

申请号：JP5098889

申请日：1989-03-04

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  TAN HIROAKI ,  HATA EIICHIRO ,  KIHARA NORIAKI

IPC: C07D519/04

Abstract: PURPOSE:To obtain the title compound such as vinblastine useful as anti-cancer drug, having antitumor activity by adding a trivalent iron source and a hydride source to a specific compound as a starting raw material in the presence of oxygen. CONSTITUTION:A trivalent iron source (preferably hydrochloride, sulfate or nitrate) and a hydride source (e.g. sodium boron hydride) are added to a compound (e.g. anhydrovinblastine) shown by formula I (R1 is H, lower alkyl or formyl; R2 is lower alkoxycarbonyl or amido; R3 is acetoxy or OH) as a starting raw material in the presence of oxygen to give the aimed compound shown by formula II (R4 is OH and R5 is OH; R4 is Et and R5 is OH). The amount the iron source added is preferably 1-2,000mols based on 1mol raw material and the amount of the hydride source added is preferably 0.1-1mol based on trivalent iron.

公开(公告)号：JPH0248582A

公开(公告)日：1990-02-19

申请号：JP19889788

申请日：1988-08-11

Applicant: MITSUI PETROCHEMICAL IND

Inventor： TAN HIROAKI ,  SAKAMOTO NAOYA ,  HATA EIICHIRO ,  ISHITOKU TAKESHI ,  KIHARA NORIAKI

IPC: C07D519/04 ,  B01J27/128 ,  C07B61/00

Abstract: PURPOSE:To industrially and efficiently obtain the subject compound useful as an antitumor agent, etc., by reacting a catharanthine with vindoline in the presence of Fe , removing or inactivating the Fe and reducing the reaction system. CONSTITUTION:Catharanthine is reacted with vindoline in nitrogen atmosphere in the presence of Fe , and then the Fe is removed by adding a basic compound such as potassium hydroxide or inactivated by adding a ligand for iron such as, for example, a lower fatty acid or a dicarboxylic acid in 0.5-200 fold mole (preferably 1-10 fold mol) based on the Fe , followed by reduction thereof the adding a reducing agent such as NaBH4 to afford the objective compound.