Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Patent
1998-03-03
1999-09-28
Geist, Gary
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
C07F 1500
Patent
active
059591331
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process for the preparation of cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers that serve as active components of carcinostatic drugs.
2. Background Art
Platinum compounds represented by formula I ##STR2## are generally known to have carcinostaticity. They have conventionally been prepared by the following steps: reacting K.sub.2 Pt(II)X.sub.4 (X is Cl or Br) with a 1,2-cyclohexanediamine isomer to form an intermediate compound represented by formula II ##STR3## dissolving the intermediate compound in water under boiling; adding thereto a solution of AgNO.sub.3 in an amount of twice the mol equivalent of the intermediate compound represented by formula II so as to cause chlorine or bromine contained in the compound to precipitate in the form of silver chloride or bromide; separating the precipitates through filtration; and adding a dibasic organic acid to the filtrate.
However, the platinum compounds represented by formula I obtained through the customary process contain as an impurity about 0.1-5% of a dihydroxoplatinum(IV) complex--a platinum compound represented by formula III--which is produced through oxidation of the platinum compounds represented by formula I. ##STR4##
SUMMARY OF THE INVENTION
In view of the foregoing, a general object of the present invention is to provide a process for a preparation of cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers that contain substantially no dihydroxoplatinum(IV) complex as an impurity.
To achieve the above object, the inventor of the present invention has conducted careful studies of a process for a preparation of cis-platinum (II) complexes of 1,2-cyclohexanediamine isomers to overcome the aforementioned problems and has developed a process which does not produce the aforementioned impurity, i.e., dihydroxoplatinum(IV) complex, by satisfactorily eliminating factors that cause oxidation during the preparation.
According to the present invention, the target compounds which serve as active components of carcinostatic drugs, i.e., cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers, are prepared from potassium tetrachloroplatinate and trans-(-)-1,2-cyclohexanediamine, and oxidation of the target complexes is prevented by the process described below.
The preparation steps of the present invention have two characteristics. Firstly, deoxygenated water is used to prevent oxidation caused by dissolved oxygen in the solution where cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers are being formed. Secondly, the oxygen content in the operational atmosphere involved in the preparation of the platinum compounds is reduced in order to eliminate possibility of direct oxidation of cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers due to atmospheric oxygen as well as to prevent degradation of deoxygenated water. Deoxygenated water degrades as it absorb oxygen.
The process of the present invention provides cis-platinum(II) complexes of 1,2-cyclohexanediamine isomers which contain substantially no physiologically active dihydroxoplatinum(IV) complex as an impurity.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
According to the process of the present invention for preparing platinum(II) complexes of 1,2-cyclohexanediamine isomers represented by formula I, there is employed deoxygenated water in all steps of preparing a platinum compound from the starting materials, i.e, potassium tetrachloroplatinate and trans-(-)-1,2-cyclohexanediarnine, and substituting nitrogen or an inert gas for air of the operational environment or alternatively degassing under vacuum to thereby produce a low-oxygen content atmosphere so as to prevent degradation of deoxygenated water and to eliminate a possibility of direct oxidation of a platinum compound due to oxygen contained in air of the operational environment.
In the process, deoxygenated water is consistently used in all steps from the placement of the starting materials, i.e., potassium tetrach
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Geist Gary
Tanaka Kikinzoku Kogyo K.K.
Vollano Jean F.
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