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【结 构 式】 
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【分子编号】11826 【品名】(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-17-(2-iodoacetyl)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one 【CA登记号】 |
【 分 子 式 】C22H29IO4 【 分 子 量 】484.37433 【元素组成】C 54.55% H 6.03% I 26.2% O 13.21% |
合成路线1
该中间体在本合成路线中的序号：(VII)Methylprednisolone suleptanate with and without radiolabeling can be prepared by two different ways: 1) The reaction of suberic acid (I) with pivaloyl chloride and triethylamine followed by condensation with N-methyltaurine sodium salt (II) gives 8-oxo-8-[N-(2-sulfoethyl)-N-methylamino]octanoic acid (III), which is treated with triethylamine and HCl, affording the corresponding triethylammonium salt (IV). The condensation of (IV) with methylprednisolone (V) by means of pivaloyl chloride and dimethylaminopyridine (DMAP) in dichloromethane yields the intermediate triethylammonium salt (VI), which is finally treated with sodium hydrogen sulfate in water. 2) The reaction of 21-deoxy-21-iodomethylprednisolone (VII) with suberic acid (I) by means of diisopropylethylamine (DEA) in DMF yields the corresponding 21-hemisuberate (VIII), which is then condensed with N-methyltaurine sodium salt (II) by means of isobutyl chloroformate and triethylamine in THF.
| 【1】 Anderson, B.D.; Conradi, R.A.; Knuth, K.E.; Strategies in the design of solution-stable, water-soluble prodrugs I: A physical-organic approach to pro-moiety selection for 21-esters of corticosteroids. J Pharm Sci 1985, 74, 365-74. |
| 【2】 Graul, A.; Leeson, J.; Castaner, J.; Methylprednisolone Suleptanate. Drugs Fut 1997, 22, 8, 833. |
| 【3】 Anderson, B.D.; Conradi, R.A. (Pharmacia Corp.); Sulfonate containing ester prodrugs of corticosteroids. JP 1984137500; US 4472392 . |
| 【4】 Pearlman, B.A. (Pharmacia Corp.); Amine salts of alkane-1,n-dicarboxylic acid mono-(2-sulfato-ethyl)amides. WO 8900558 . |
| 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) | 11820 | Suberic acid; Cork acid; Octanedioic acid | 505-48-6 | C8H14O4 | 详情 | 详情 |
| (II) | 11821 | sodium 2-(methylamino)-1-ethanesulfonate | 4316-74-9 | C3H8NNaO3S | 详情 | 详情 |
| (III) | 11822 | 7-[N-Methyl-N-(2-sulfoethyl)carbamoyl]heptanoic acid disodium salt | C11H19NNaO6S | 详情 | 详情 | |
| (IV) | 11823 | N,N-diethyl-1-ethanaminium 2-[(7-carboxyheptanoyl)(methyl)amino]-1-ethanesulfonate | C17H36N2O6S | 详情 | 详情 | |
| (V) | 10394 | Methylprednisolone | 83-43-2 | C22H30O5 | 详情 | 详情 |
| (VI) | 11825 | N,N-diethyl-1-ethanaminium 3-[(8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoyl)(methyl)amino]-1-propanesulfonate | C40H66N2O10S | 详情 | 详情 | |
| (VII) | 11826 | (6S,8S,9S,10R,11S,13S,14S,17R)-11,17-Dihydroxy-17-(2-iodoacetyl)-6,10,13-trimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C22H29IO4 | 详情 | 详情 | |
| (VIII) | 11827 | sodium 8-[2-[(6S,8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-6,10,13-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-8-oxooctanoate | C30H41NaO8 | 详情 | 详情 |