公开(公告)号：JPH04164087A

公开(公告)日：1992-06-09

申请号：JP28842690

申请日：1990-10-29

Applicant: MITSUI PETROCHEMICAL IND

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

IPC: C07D519/04 ,  A61K31/475 ,  A61P35/00

Abstract: PURPOSE:To obtain the subject compound useful as an anticancer agent by adding a trivalent iron ion source, etc., to anhydrovinblastine in the presence of oxygen, completing reaction, then adding a tridentate ligand to the iron ions in the reaction solution and carrying out ligand exchange. CONSTITUTION:A trivalent iron ion source (preferably hydrochloride, sulfate or nitrate), an oxalate ion source and a hydride source (e.g. sodium boron hydride) are added to anhydrovinblastine in the presence of oxygen and the resultant product is separated. In the process, a tridentate ligand (preferably trisodium citrate) is added to the iron ions in the reaction solution to carry out ligand exchange after completing the reaction. The pH is then preferably regulated to >=6.5 and the formed product is subsequently extracted with an organic solvent (preferably 1,2-dichloroethane, etc.) immiscible with the aforementioned reaction solution. The resultant extract is then subjected to column chromatography to afford the objective compound.

公开(公告)号：JPH04164086A

公开(公告)日：1992-06-09

申请号：JP28842590

申请日：1990-10-29

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  KIHARA NORIAKI

IPC: C07D519/04 ,  A61K31/475 ,  A61P35/00

Abstract: PURPOSE:To purify vinblastine useful as an anticancer agent by dissolving a dimeric alkaloid mixture containing the vinblastine and leurosidine in an acidic aqueous solution and selectively extracting the dimeric alkaloid mixture containing the vinblastine other than the leurosidine with a halogenated hydrocarbon-based organic solvent. CONSTITUTION:A dimeric alkaloid mixture containing vinblastine and leurosidine is dissolved in an acidic aqueous solution (preferably sodium dihydrogenphosphate, potassium dihydrogenphosphate, etc., providing a buffer solution at pH 2-5) and the dimeric alkaloid containing the vinblastine other than the leurosidine is extracted with a halogenated hydrocarbon-based organic solvent (preferably trichloroethylene or methylchloroform) to selectively separate the leurosidine. Thereby, the vinblastine is purified.

公开(公告)号：JPH0395188A

公开(公告)日：1991-04-19

申请号：JP23165989

申请日：1989-09-08

Applicant: MITSUI PETROCHEMICAL IND

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

IPC: C07D519/04 ,  C07B61/00

Abstract: PURPOSE:To obtain the subject compound useful as a carcinostatic agent on an industrial scale at a low cost by reacting a specific compound with a hydride source in the presence of oxygen and an Fe ion source under specific condition. CONSTITUTION:The objective compound of formula II (one of R and R is hydroxy and the other is ethyl) is produced e.g. by continuously supplying (A) a solution produced by dissolving a compound of formula I (R is H, lower alkyl or formyl; R is lower alkoxycarbonyl or amido; R is acetoxy or hydroxy) and oxygen in a solvent such as water, (B) a solution produced by dissolving 0.1-10,000 mol (based on 1mol of the compound of formula I) of an Fe ion source in water, etc., and adding 0.1-3mol (based on 1mol of the Fe ion source) of an oxalic acid ion source or malonic acid ion source, 0.1-100mol of an inorganic anion source and 0.01-10mol of a pyridine derivative to the Fe ion source solution and (C) an aqueous solution of a halide source (0.05-10mol per 1mol of Fe ) such as sodium borohydroxide from a column and contacting the solutions with each other at -20 to +10 deg.C for 0.1sec to 60min.

公开(公告)号：JPH02231494A

公开(公告)日：1990-09-13

申请号：JP5099189

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 having antitumor activity and useful as an anticancer agent by adding oxalic acid (salt), etc., inorganic anion source, trivalent iron source and hydride source to a specific compound used as a starting raw material in the presence of oxygen. CONSTITUTION:Oxalic acid (salt) and/or malonic acid (salt), inorganic anion source (preferably Cl , Br , I , SO, etc., except such an inorganic anion as to produce an insoluble iron salt such as CO), trivalent iron source (preferably hydrochloric acid salt, sulfuric acid salt or nitric acid salt) and hydride source (e.g. sodium borohydride) are added to a compound (e.g. anhydro-vinblastine) expressed by formula I (R1 is H, lower alkyl or formyl; R2 is lower alkoxycarbonyl or amide; R3 is acetoxy or OH) and used as a starting raw material in the presence of oxygen to provide the aimed compound expressed by formula II (R4 is OH and R5 is Et or R4 is Et and R5 is OH).

公开(公告)号：JPH0248583A

公开(公告)日：1990-02-19

申请号：JP19889888

申请日：1988-08-11

Applicant: MITSUI PETROCHEMICAL IND

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

IPC: C07D519/04 ,  B01J27/128

Abstract: PURPOSE:To efficiently obtain the subject compound in high yield by reacting a catharanthine with vindoline in the presence of Fe , making oxygen and a dicarboxylic acid or a derivative thereof existent therein and then adding a hydride source thereto. CONSTITUTION:A catharanthine is reacted with vindoline in a nitrogen atmosphere in the presence of Fe , added with a salt of dicarboxylic acid and derivative thereof (preferably ammonium oxalate, etc.) in 1-10 fold moles (based on the Fe ). Then the system is changed into an oxygen atmosphere and 0.05-10 fold mol (based on the Fe ) of a hydride source (example; sodium hydrogen borate) and a solvent such as acetone are added to carry out reaction preferably at -10 to 10 deg.C. After the reaction, the product is basified by treating with ammonia and extracted with an organic solvent to afford the objective compound.

公开(公告)号：JPH01301629A

公开(公告)日：1989-12-05

申请号：JP13227988

申请日：1988-05-30

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  SHIMAMOTO KENJI ,  FUJIMOTO TADAAKI ,  TANIGUCHI KATSUO

IPC: B01J23/16 ,  B01J27/02 ,  B01J27/18 ,  B01J27/188 ,  C07B61/00 ,  C07C1/00 ,  C07C5/41 ,  C07C15/24 ,  C07C67/00

Abstract: PURPOSE:To produce naphthalenes in high selectivity and yield, by reacting substituted benzenes using a catalyst consisting of a compound oxide of at least one (except oxygen) selected from group VIb elements and indium. CONSTITUTION:Substituted benzenes [e.g. 2,5-dimethyl-(2-butenyl)benzene] expressed by the formula (R is 1-3C alkyl; n indicates the number of groups R and an integer of 0-2; m is an integer of 4-6; p is an integer of 0-2) are reacted in the presence of a catalyst containing a compound oxide [e.g. (NH4)2SO4, In(NO3)3 or (NH4)3PO4] of at least one (except oxygen) selected from group VIb elements and indium or further containing phosphorus oxide as a catalyst to afford naphthalenes (e.g. 2,6-dimethylnaphthalene).

公开(公告)号：JPH04120056A

公开(公告)日：1992-04-21

申请号：JP23803890

申请日：1990-09-07

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  ISHIGURO MASAHARU

IPC: C07D223/06 ,  C07C211/52 ,  C07C217/56 ,  C07C225/16 ,  C07D207/08 ,  C07D207/12 ,  C07D207/14 ,  C07D211/30 ,  C07D211/42 ,  C07D211/44 ,  C07D211/56 ,  C07D223/08 ,  C07D223/12 ,  C07D225/02

Abstract: PURPOSE:To obtain the subject compound widely useful as intermediates for pharmaceuticals and agricultural chemicals in high purity by treating a crude reaction product of the subject compound containing dimer as an impurity with activated carbon in a solvent, thereby efficiently removing the impurity. CONSTITUTION:A compound of formula III or formula IV or their salt containing a compound of formula I or formula II (R is H or lower alkyl; X is halogen; Y is O, CO or NHCO; n and m are 1-6) or their salt is treated with activated carbon in a solvent such as lower alcohol or alkyl halide to remove the compound of formula I or formula II or their salt. When the raw material is the compound of formula III or formula IV, water or a mixture of water and a water-soluble organic solvent can be used as the solvent. The activated carbon is preferably powdery charcoal and its amount is 0.1-20wt.%, preferably 0.5-10wt.% based on the substrate.

公开(公告)号：JPH0649008A

公开(公告)日：1994-02-22

申请号：JP5288992

申请日：1992-03-11

Applicant: MITSUI PETROCHEMICAL IND

Inventor： KONDO MASAHIRO ,  TANAKA MICHIO ,  SAKAMOTO NAOYA ,  OYOSHI HAJIME

IPC: C07C227/42 ,  C07C227/02 ,  C07C227/10 ,  C07C229/52

Abstract: PURPOSE:To produce a keto-acid in high selectivity with suppressing by-products by selecting the amount of a solvent used so as to precipitate the formed keto- acid and to advance reaction in a slurried state in the reaction between a m- aminophenol derivative and phthalic anhydride. CONSTITUTION:A m-aminophenol derivative of formula I (R and R are 1-6C alkyl or 4-8C cycloalkyl)(e.g. N,N-diethyl-m-aminophenol) is reacted with phthalic anhydride to give a keto-acid of formula II (e.g. 4-N,N-diethylamino-2-hydroxy-2'- carboxybenzophenone). In the reaction, 0.5-3 pts.wt. reaction solvent is used based on 1 pt.wt. m-aminophenol derivative in order to precipitate the keto-acid formed by the reaction and the reaction is carried out in a slurried state. Benzene, toluene, xylene, ethers, etc., are used as the reaction solvent. Secondary crystallization can be done under pressure depending upon the amount of the keto-acid in the solvent. The high-purity keto-acid is obtained in high yield.

公开(公告)号：JPH05339220A

公开(公告)日：1993-12-21

申请号：JP15250192

申请日：1992-06-11

Applicant: MITSUI PETROCHEMICAL IND

Inventor： SAKAMOTO NAOYA ,  OYOSHI HAJIME

IPC: C07C227/40 ,  C07C227/42 ,  C07C229/52

Abstract: PURPOSE:To industrially and effectively remove by-produced colored substances and purify the keto acid derivative by adding a hydrogenation catalyst to a reaction solvent containing the crude keto acid derivative obtained from a N,N-dialkyl-m-aminophenol and phthalic acid and subsequently hydrogenating the crude keto acid derivative. CONSTITUTION:When a keto acid derivative of the formula (R , R are 1-6C alkyl) is obtained by reacting a N,N-dialkyl-m-aminophenol with phthalic anhydride and subsequently purified, the crude colored keto acid derivative of the formula containing a small amount of colored substances such as rhodamine is dissolved in a reaction solvent, mixed with a hydrogenation catalyst, hydrogenated in a reaction solvent and subsequently subjected to recrystallization, etc., to recover the keto acid derivative from the reaction solution. The method is advantageous, since an alkali, etc., is not used, and neutralized effluent water, etc., is not discharged. The keto acid derivative having a good color tone can be obtained by the foregoing simple process.

公开(公告)号：JPH04169587A

公开(公告)日：1992-06-17

申请号：JP29351290

申请日：1990-11-01

Applicant: MITSUI PETROCHEMICAL IND

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

IPC: C07D519/04 ,  A61K31/475 ,  A61P35/00

Abstract: PURPOSE:To obtain a deoxyvinblastine, etc., useful as a carcinostatic agent on an industrial scale in high yield at a low cost by reducing a dimer alkaloid in the presence of a ferric ion source and a hydride source. CONSTITUTION:The objective compound of formula II can be produced by using a compound of formula I (R1 is H, lower alkyl or formyl; R2 is lower alkoxycarbonyl; R3 is acetoxy or OH) as a starting raw material and reducing the compound by adding a ferric ion source (preferably hydrochloride, sulfate, nitrate or ferric ammonium oxalate) and a hydride source (e.g. sodium borohydride) preferably in the presence of an inert gas while adding an oxalate ion source to the reaction system. The amounts of the ferric ion source and the hydride source are preferably 1-2,000mol and 0.1-50mol based on 1mol of the raw material, respectively.