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【结 构 式】 
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【药物名称】Eptaplatin, Heptaplatin, NSC-644591, NSC-D-644591, SKI-2053R, Sunpla 【化学名称】cis-[(4R,5R)-2-Isopropyl-1,3-dioxolane-4,5-bis(methylamine)-N,N'][malonato(2-)-O,O']platinum 【CA登记号】146665-77-2 【 分 子 式 】C11H20N2O6Pt 【 分 子 量 】471.38185 |
【开发单位】SK Chemicals (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA-Damaging Drugs, Platinum Complexes |
合成路线1
Reaction of D-tartaric acid (I) with EtOH in the presence of an acid catalyst gives diethyl D-tartrate (II), which is treated with isobutyraldehyde and anhydrous CuSO4 in the presence of methanesulfonic acid yielding diethyl 2,3-O-isobutylidene-D-tartrate (III). The 1,3-dioxolane diester (III) was then reduced with LAH to afford (4R,5R)-4,5-bis(hydroxymethyl)-2-isopropyl-1,3-dioxolane (IV), which is treated with methanesulfonyl chloride in pyridine yielding (4R,5R)-4,5-bis(methylsulfonyloxymethyl)-2-isopropyl-1,3-dioxolane (V). The bis(methanesulfonate) (V) is reacted with NaN3 in DMF to give (4R,5R)-4,5-bis(azidomethyl)-2-isopropyl-1,3-dioxolane (VI), which is reduced with hydrogen in the presence of 10% Pd/C in EtOH to afford (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane (VII). The diamine (VII) is reacted with an equimolar amount of in situ generated K2PtI4 to afford cis-diiodo[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) (VIII), which is finally treated with malonic acid disilver salt in H2O to obtain (IX).
| 【1】 Kim, Y.; Rim, J.; Yoo, K.; Kim, G.; Gam, J.; Kim, K.H.; Kim, D.-K.; Song, S.; Synthesis of carbon-14 labelled cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane] platinum(II) (SKI 2053R). J Label Compd Radiopharm 1994, 34, 2, 157-64. |
| 【2】 Kim, D.-K.; Kim, K.H.; SKI-2053R. Drugs Fut 1995, 20, 11, 1128. |
| 【3】 Kim, D.-K.; Cho, Y.-B.; Park, J.-G.; Tai, J.-H.; Kim, K.H.; Hong, W.-S.; Kim, H.-T.; Kim, G.; Gam, J.; Synthesis and antitumor activity of a series of [2-substituted-4,5-bis(aminomethyl)-1,3-dioxolane]platinum(II) complexes. J Med Chem 1994, 37, 10, 1471-85. |
| 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) | 16695 | (2S,3S)-2,3-dihydroxybutanedioic acid; D-(-)-Tartaric Acid; D-Tartaric Acid; (2S,3S)-2,3-dihydroxysuccinic acid | 147-71-7 | C4H6O6 | 详情 | 详情 |
| (II) | 16696 | Diethyl L-(+)-Tartrate; diethyl (2S,3S)-2,3-dihydroxybutanedioate | 87-91-2 | C8H14O6 | 详情 | 详情 |
| (III) | 16697 | diethyl (4S,5S)-2-isopropyl-1,3-dioxolane-4,5-dicarboxylate | C12H20O6 | 详情 | 详情 | |
| (IV) | 16698 | [(4R,5R)-5-(hydroxymethyl)-2-isopropyl-1,3-dioxolan-4-yl]methanol | C8H16O4 | 详情 | 详情 | |
| (V) | 16699 | (4R,5R)-2-isopropyl-4,5-bis([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-1,3-dioxolane | C14H28O4S2 | 详情 | 详情 | |
| (VI) | 16700 | 1-[[(4R,5R)-2-isopropyl-5-(triazanylmethyl)-1,3-dioxolan-4-yl]methyl]triazane | C8H22N6O2 | 详情 | 详情 | |
| (VII) | 16701 | [(4R,5R)-5-(aminomethyl)-2-isopropyl-1,3-dioxolan-4-yl]methylamine; [(4R,5R)-5-(aminomethyl)-2-isopropyl-1,3-dioxolan-4-yl]methanamine | C8H18N2O2 | 详情 | 详情 | |
| (VIII) | 16702 | cis-diiodo[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum; cis-[(4R,5R)-2-isopropyl-1,3-dioxolane-4,5-dimethanamine-N,N']diiodoplatinum | C8H16I2N2O2Pt | 详情 | 详情 | |
| (IX) | 16703 | malonic acid disilver salt | C3H2Ag2O4 | 详情 | 详情 |