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【结 构 式】 
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【分子编号】51693 【品名】dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate 【CA登记号】10025-99-7 |
【 分 子 式 】Cl4K2Pt 【 分 子 量 】415.0874 【元素组成】Cl 34.16% K 18.84% Pt 47% |
合成路线1
该中间体在本合成路线中的序号：(V)Enloplatin can be obtained by two related ways: 1) The cyclization of 2,2'-dichloroethylether (I) with malonodinitrile (II) by means of K2CO3 in refluxing acetonitrile gives tetrahydropyran-4,4-dicarbonitrile (III), which is reduced with BH3 in THF yielding tetrahydropyran-4,4-dimethamine (IV). The reaction of (IV) with potassium tetrachloroplatinate (V) affords dichloro(tetrahydropyran-4,4-dimethanamine-N,N')platinum(II) (VI), which is finally condensed with cyclobutane-1,1-dicarboxylic acid silver salt (VIII) in water. 2) The reaction of potassium tetrachloroplatinate (V) with DMSO gives dichloro-bis(dimethylsulfoxide)platinum(II) (VII), which is condensed with silver salt (VIII) to afford (1,1-cyclobutane-dicarboxylato-O,O')bis(dimethylsulfoxide)platinum(II) (IX), which is finally treated with diamine (IV) as before.
| 【1】 Child, R.G.; Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); (Gem-heterocyclodimethanamine-N,N')platinum complexes. EP 0232784; US 4880790 . |
| 【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 . |
| 【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015. |
| 【4】 Castaner, J.; Prous, J.; Enloplatin. Drugs Fut 1992, 17, 6, 459. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 12060 | Bis(2-chloroethyl) ether; 1-Chloro-2-(2-chloroethoxy)ethane; 2,2'-Dichlorodiethyl ether | 111-44-4 | C4H8Cl2O | 详情 | 详情 |
| (II) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (III) | 12062 | Tetrahydro-4H-pyran-4,4-dicarbonitrile | C7H8N2O | 详情 | 详情 | |
| (IV) | 12063 | [4-(Aminomethyl)tetrahydro-2H-pyran-4-yl]methanamine; [4-(Aminomethyl)tetrahydro-2H-pyran-4-yl]methylamine | C7H16N2O | 详情 | 详情 | |
| (V) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (VI) | 12064 | 4,4-Bis(aminomethyl)tetrahydropyran dichloro platinum complex | C7H16Cl2N2OPt | 详情 | 详情 | |
| (VII) | 61657 | dichloroplatinum | Cl2Pt | 详情 | 详情 | |
| (VIII) | 12065 | Bis(dimethylsulfoxide-S,S')dichloroplatinum | C6H6Ag2O4 | 详情 | 详情 | |
| (IX) | 12066 | Cyclobutane-1,1-dicarboxylic acid platinum salt | C6H6O4Pt | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Zeniplatin can be obtained by two related ways: 1) The reaction of dimethylsulfoxide with potassium tetrachloroplatinate (I) gives bis(dimethylsulfoxide-S,S')dichloroplatinum (II), which is then condensed with silver cyclobutane-1,1-dicarboxylate (III) in water to yield bis(dimethylsulfoxide-S,S')(1,1-cyclobutanedicarboxylato-O,O')platinum (IV). Finally, this compound is treated with 2,2-bis(aminomethyl)-1,3-propanediol (V) in refluxing water. 2) The reaction of potassium tetrachloroplatinate (I) with diamine (V) in water gives [2,2-bis(aminomethyl)-1,3-propanediol-N,N']dichloroplatinum (IV), which is treated with the silver salt (III) as before. The diamine (V) is prepared by reaction of 2,2-bis(bromomethyl)-1,3-propanediol (VII) with sodium azide in hot DMF to give 2,2-bis(azidomethyl)-1,3-propanediol (VIII), which is then reduced with hydrogen over Pt.
| 【1】 Grassing Child, R.; Bitha, P.; Hlavka, J.J.; Lin, Y. (Zyma); [2,2-Bis(aminomethyl)-1,3-propanediol-N,N']platinum complexes. AU 8432572; EP 0140830; ES 8802308; GB 2145720; JP 1985149581; US 4665202 . |
| 【2】 Bitha, P.; Hlavka, J.J.; Lin, Y. (American Cyanamid Co.); Synthesis of cisplatinum analogs. EP 0296321 . |
| 【3】 Carvajal, S.G.; Citarella, R.V.; Bitha, P.; et al.; Water-soluble third generation antitumor Pt complexes, [2,2-bis(aminomethyl)-1,3-propanediol-N,N']- [1,1-cyclobutanedicarboxylato(2-)-O,O']Pt(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O']-[tetrahydro-4H-pyran-4,4-dimethanamine-N,N']Pt(II). J Med Chem 1989, 32, 8, 2015. |
| 【4】 Prous, J.; Castaner, J.; Zeniplatin. Drugs Fut 1992, 17, 6, 471. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (II) | 61657 | dichloroplatinum | Cl2Pt | 详情 | 详情 | |
| (III) | 12065 | Bis(dimethylsulfoxide-S,S')dichloroplatinum | C6H6Ag2O4 | 详情 | 详情 | |
| (IV) | 12069 | Cyclobutane-1,1-dicarboxylic acid platinum salt | C6H6O4Pt | 详情 | 详情 | |
| (V) | 12070 | 2,2-Bis(aminomethyl)-1,3-propanediol | C5H14N2O2 | 详情 | 详情 | |
| (VI) | 12071 | 2,2-Bis(hydroxymethyl)propane-1,3-diamine dichloro platinum complex | C5H14Cl2N2O2Pt | 详情 | 详情 | |
| (VII) | 12072 | Dibromoneopentyl glycol; 2,2-Bis(bromomethyl)-1,3-propanediol | 3296-90-0 | C5H10Br2O2 | 详情 | 详情 |
| (VIII) | 12073 | 2,2-Bis(azidomethyl)-1,3-propanediol | C5H10N6O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)The platinum nitrate derivative (X) was prepared by two related procedures. Halogen-exchange of potassium tetrachloroplatinate (V) with KI produced the tetraiodoplatinate (VI), which was subsequently reacted with trans-1,2-diaminocyclohexane (VII) to give the diamino chelate (VIII). Alternatively, diamine (VII) was reacted with tetrachloroplatinate (V), yielding chelate (IX). Treatment of either iodo compound (VIII) or its analogous chloride (IX) with silver nitrate furnished the dinitrate compound (X). Finally, the diacid formed by basic hydrolysis of anhydride (IV) was in situ complexed with the platinum compound (X) to generate the title platinum complex.
| 【1】 Lin, G.; To, K.K.W.; Wang, X.; Han, X.; Au-Yeung, S.C.F.; Ho, Y.-P.; Potential new antitumor agents from an innovative combination of demethylcantharidin, a modified traditional Chinese medicine, with a platinum moiety. J Med Chem 2001, 44, 13, 2065. |
| 【2】 Ho, Y.P.; Au-Yeung, S.C.F.; Jiang, T.; Han, X.; Wang, X.; Lin, G.; Lu, S. (Chinese University of Hong Kong); Synthesis of platinum complexes and uses thereof. WO 9849174 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 49888 | 4,10-Dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C8H8O4 | 详情 | 详情 | |
| (V) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (VI) | 51694 | dipotassium tetraiodoplatinate(2-);potassium tetraiodoplatinate(II);Potassium tetraiodoplatinate | 14708-56-6 | I4K2Pt | 详情 | 详情 |
| (VII) | 11130 | (1R,2R)-1,2-cyclohexanediamine; (1R,2R)-2-aminocyclohexylamine; cis-1,2-Diaminocyclohexane | 20439-47-8 | C6H14N2 | 详情 | 详情 |
| (VIII) | 50042 | C6H14I2N2Pt | 详情 | 详情 | ||
| (IX) | 23063 | (R,R)-Cyclohexane-1,2-diamine dichloro platinum complex | C6H14Cl2N2Pt | 详情 | 详情 | |
| (X) | 19480 | (R,R)-Cyclohexane-1,2-diamine dinitrato platinum complex | n/a | C6H14N4O6Pt | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)Substitution of chlorine with iodine in potassium tetrachloroplatinate (I) by treatment with KI in water results in potassium tetraiodoplatinate (II), which by reaction with cyclohexylamine (III) yields cis-di(cyclohexylamine)diiodoplatinium (IV). Reaction of complex (IV) with HClO4 in H2O/EtOH furnishes dimer (V), which is then treated with NH4OH in H2O affording cis-ammine(cyclohexylamine) diiodoplatinium (VI). Nitration of complex (VI) with AgNO3 in H2O followed by chlorination with HCl gives cis-amminechloro-(cyclohexylamine)platinium (VII) . Alternatively, treatment of cisplatin (VIII) with Et4NCl in dimethylacetamide at 100 °C followed by ion exchange by DOWEX 50WX8 and HCl leads to amminetrichloroplatinum (IX), which is then treated with KCl, giving potassium(SP-4-2)-amminetrichloroplatinate (X). Subsequent reaction of compound (X) with cyclohexylamine (III) in the presence of NaI in water furnishes (SP-4-3)-amminechloro(cyclohexanamine)iodoplatinum (XI), which by subsequent nitration and chlorination with AgNO3 in water and treatment with HCl affords complex (VII) . Then, compound (VII) is submitted to hydroxylation with H2O2 in water to give (OC-6-43)-amminedichloro(cyclohexylamine)dihydroxyplatinum (XII), which is finally acetylated with Ac2O in CH2Cl2 .
| 【1】 Khokhar, A.R., Deng, Y., Al-Baker, S., Yoshida, M., Siddik, Z.H. Synthesis and antitumor activity of ammine/amine platinum (II) and (IV) complexes. J Inorg Biochem 1993, 51(3): 677-87. |
| 【2】 Ciandomenico, C.M., Abrams, M.J., Murrer, B.A. et al. Carboxylation of kinetically inert platinum (IV) hydroxy complexes. An entr.acte.ee into orally active platinum (IV) antitumor agents. Inorg Chem 1995, 34(5): 1015-21. |
| 【3】 Abrams, M.J., Giandomenico, C.M., Murrer, B.A., Vollano, J.F. (Johnson Matthey plc). Pt(IV) complexes. AU 8928971, EP 0328274, JP 1989294684. |
| 【4】 Abrams, M.J., Giandomenico, C., Murrer, B.A., Vollano, J.F. (Johnson &Johnson). Pt(IV) complexes. US 5072011. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 51693 | dipotassium tetrachloroplatinate(2-);potassium tetrachloroplatinate(II);potassium tetrachloroplatinate | 10025-99-7 | Cl4K2Pt | 详情 | 详情 |
| (II) | 51694 | dipotassium tetraiodoplatinate(2-);potassium tetraiodoplatinate(II);Potassium tetraiodoplatinate | 14708-56-6 | I4K2Pt | 详情 | 详情 |
| (III) | 17966 | cyclohexanamine; cyclohexyl amine; cyclohexylamine | 108-91-8 | C6H13N | 详情 | 详情 |
| (IV) | 69489 | cis-di(cyclohexylamine)diiodoplatinium | C12H26I2N2Pt | 详情 | 详情 | |
| (V) | 69490 | (cyclohexylamino)platinum(III) iodide | C12H26I4N2Pt2 | 详情 | 详情 | |
| (VI) | 69491 | cis-ammine(cyclohexylamine)diiodoplatinium | C6H16I2N2Pt | 详情 | 详情 | |
| (VII) | 69492 | cis-amminechloro-(cyclohexylamine)platinium | C6H16Cl2N2Pt | 详情 | 详情 | |
| (VIII) | 51698 | dichloroplatinum diammoniate | H6Cl2N2Pt | 详情 | 详情 | |
| (IX) | 69493 | amminetrichloroplatinum | H4Cl3NPt | 详情 | 详情 | |
| (X) | 69494 | potassium (SP-4-2)-amminetrichloroplatinate | H3Cl3KNPt | 详情 | 详情 | |
| (XI) | 69495 | (SP-4-3)-amminechloro(cyclohexanamine)iodoplatinum | C6H16ClIN2Pt | 详情 | 详情 | |
| (XII) | 69496 | (OC-6-43)-amminedichloro(cyclohexylamine)dihydroxyplatinum | C6H18Cl2N2O2Pt | 详情 | 详情 |