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【结 构 式】 
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【分子编号】14612 【品名】(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid 【CA登记号】 |
【 分 子 式 】C20H26O5 【 分 子 量 】346.42344 【元素组成】C 69.34% H 7.56% O 23.09% |
合成路线1
该中间体在本合成路线中的序号：(II)The oxidation of 11beta,17,21-trihydroxypregnan-1,4-diene-3,20-dione (I) with sodium metaperiodate in THF/methanol gives 11beta,17alpha-dihydroxy-3-oxoandrosta-1,4-diene-17beta-carboxylic acid (II), which is treated with ethyl chloroformate and triethylamine in dichloromethane yielding 17alpha-(ethoxycarbonyloxy)-11beta-hydroxy-3-oxoandrosta-1,4-diene-17beta-carboxylic acid (III). Finally, this compound is esterified with chloromethyl iodide and NaOH in methanol/water.
| 【1】 Graul, A.; Martin, L.; Castaner, J.; Loteprednol Etabonate. Drugs Fut 1997, 22, 10, 1086. |
| 【2】 Bodor, N.S. (N.S. Bodor); Steroids with antiinflammatory activity. BE 0889563; US 4996335 . |
| 【3】 Druzgala, P.; Hochhaus, G.; Bodor, N.; Soft drugs - 10. Blanching activity and receptor binding affinity of a new type of glucocorticoid: Loteprednol etabonate. J Steroid Biochem Mol Biol 1991, 38, 2, 149-154. |
| 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) | 13538 | (8S,9S,10R,11S,13S,14S,17R)-17-Glycoloyl-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one; Prednisolone | 50-24-8 | C21H28O5 | 详情 | 详情 |
| (II) | 14612 | (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C20H26O5 | 详情 | 详情 | |
| (III) | 14613 | (8S,9S,10R,11S,13S,14S,17R)-17-[(ethoxycarbonyl)oxy]-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C23H30O7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The oxidative cleavage of prednisolone (I) using sodium metaperiodate produces carboxylic acid (II). Regioselective esterification of diol (II) with dichloroacetyl chloride (III) under phase-transfer conditions gives the 17-ester (IV). The title ethyl ester is then obtained by esterification of (IV) with iodoethane in the presence of NaHCO3 and tetrabutylammonium hydrogensulfate.
| 【1】 Bodor, N.S. (Soft Drugs, Inc.); Androstene derivs.. WO 9742214 . |
| 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) | 13538 | (8S,9S,10R,11S,13S,14S,17R)-17-Glycoloyl-11,17-dihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one; Prednisolone | 50-24-8 | C21H28O5 | 详情 | 详情 |
| (II) | 14612 | (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C20H26O5 | 详情 | 详情 | |
| (III) | 17829 | 2,2-dichloroacetyl chloride; dichloroacetyl chloride | 79-36-7 | C2HCl3O | 详情 | 详情 |
| (IV) | 58347 | (8S,9S,10R,11S,13S,14S,17R)-17-[(2,2-dichloroacetyl)oxy]-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid | C22H26Cl2O6 | 详情 | 详情 |