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【结 构 式】 
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【分子编号】38915 【品名】2-[(10R,11S,13S,16R,17S)-11-hydroxy-16,17-bis(isobutyryloxy)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 2-methylpropanoate 【CA登记号】 |
【 分 子 式 】C33H46O9 【 分 子 量 】586.72284 【元素组成】C 67.56% H 7.9% O 24.54% |
合成路线1
该中间体在本合成路线中的序号：(III)The acylation of 11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione (I) with isobutyric anhydride in pyridine gives the 16,17,21-triester (III), which is condensed with cyclohexanecarbaldehyde (IV) by means of HCl and HClO4 in dioxane yielding the cyclic ketal (Va-b) as a diastereomeric mixture. Finally, this mixture is resolved by preparative HPLC over Lichrosorb RP-18 affording the desired (R)-isomer, the target compound. Alternatively, the monoacylation of the ketal 11beta,16alpha,17alpha,21-tetrahydroxypregan-1,4-diene-3,20-dione 16,17-O-cyclohexylmethylene ketal (VI) with isobutyric anhydride (II) by means of K2CO3 in acetone gives the previously described diastereomeric mixture (Va-b), which is resolved by crystallization in ethanol/water.
| 【1】 Calatayud, J.; Conde, J.R.; Luna, M. (Byk Elmu SA); Acetals and esters of 16alpha-hydroxyprednisolone and fluocinolone. BE 1005876; CH 683343; DE 4129535; ES 2034893; FR 2666585; GB 2247680; JP 1992257599; US 5482934 . |
| 【2】 Gutterer, B.; Amschler, H.; Flockerzi, D. (Byk Gulden Lomberg Chemische Fabrik GmbH); Process for R-epimer enrichment of 16,17-acetal derivs. of 21-acyloxy pregnan-1,4-dien-11beta,16alpha,17alpha-triol-3,20-dione derivs.. DE 19635498; WO 9809982 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 38916 | 2-[(4aR,5S,6aS,8S,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate | C32H44O7 | 详情 | 详情 | |
| (Vb) | 38917 | 2-[(4aR,5S,6aS,8R,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate | C32H44O7 | 详情 | 详情 | |
| (I) | 32675 | (8S,9S,10R,11S,13S,14S,16R,17S)-17-glycoloyl-11,16,17-trihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H28O6 | 详情 | 详情 | |
| (II) | 22334 | 1-methylpropionic anhydride | 97-72-3 | C8H14O3 | 详情 | 详情 |
| (III) | 38915 | 2-[(10R,11S,13S,16R,17S)-11-hydroxy-16,17-bis(isobutyryloxy)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 2-methylpropanoate | C33H46O9 | 详情 | 详情 | |
| (IV) | 33694 | cyclohexanecarbaldehyde | 2043-61-0 | C7H12O | 详情 | 详情 |
| (VI) | 38918 | (4aR,5S,6aS,6bS,9aR)-8-cyclohexyl-6b-glycoloyl-5-hydroxy-4a,6a-dimethyl-4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-dodecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-2-one | C28H38O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)
| 【1】 应明华，关定伟，陈鸿鹏．2005．一锅法制备淡尼橙龙衍生物，发明专利公开说明书．CN1699395A |
| 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) | 32675 | (8S,9S,10R,11S,13S,14S,16R,17S)-17-glycoloyl-11,16,17-trihydroxy-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H28O6 | 详情 | 详情 | |
| (II) | 22334 | 1-methylpropionic anhydride | 97-72-3 | C8H14O3 | 详情 | 详情 |
| (III) | 38915 | 2-[(10R,11S,13S,16R,17S)-11-hydroxy-16,17-bis(isobutyryloxy)-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl 2-methylpropanoate | C33H46O9 | 详情 | 详情 | |
| (V) | 38917 | 2-[(4aR,5S,6aS,8R,9aR)-8-cyclohexyl-5-hydroxy-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,9a,10,10a,10b,11,12-dodecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-6-yl]-2-oxoethyl 2-methylpropanoate | C32H44O7 | 详情 | 详情 |