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【结 构 式】 
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【分子编号】21359 【品名】(10R,11S,13S,16R,17S)-11-hydroxy-10,13-dimethyl-3-oxo-17-[3-(tetrahydro-2H-pyran-2-yloxy)propanoyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-16-carbonitrile 【CA登记号】 |
【 分 子 式 】C28H37NO5 【 分 子 量 】467.60552 【元素组成】C 71.92% H 7.98% N 3% O 17.11% |
合成路线1
该中间体在本合成路线中的序号：(IV)P16CM is synthesized from prednisolone (I) via the key 16,17-dehydro intermediate (III). The compound (III) is prepared by literature procedures from prednisolone by its conversion to prednisolone 17,21-diacetate (II), followed by a potassium acetate-induced acyloxy elimination reaction. Michael addition to (III) with KCN provides the 21-acetoxy-16alpha-cyano compound, which is deprotected at C-21 and reprotected with a base-stable tetrahydropyranyl (THP) group to provide (IV). A base hydrolysis of (IV), followed by deprotection at C-21 and esterification at the 16-carboxylate, gives (V), the 17-desoxy analogue of P16CM. 17alpha-Hydroxylation of (V) via the intermediate 17,20-enol acetate, using dilute peroxyacetic acid solution at low temperature, yields P16CM.
| 【1】 Salce, L.; Hazen, G.C.; Schoenwaldt, E.F.; J Org Chem 1970, 35, 1681. |
| 【2】 Teraporewala, I.B.; Kim, H.P.; Heiman, A.S.; Lee, H.J.; A novel class of local antiinflammatory steroids. 1st communication: Analogues of methyl 11beta,17alpha,21-trihydroxy-3,20-dioxopregna-1,4-diene-16alpha -carboxylate. Arzneim-Forsch Drug Res 1989, 398, 21. |
| 【3】 Lee, H.J. (Florida Agricultural and Mechanical Univ.); Anti-inflammatory carboxy pregnane derivatives. US 4762919; WO 8705028 . |
| 【4】 Lee, H.-J.; Taraporewala, I.B.; P16CM. Drugs Fut 1989, 14, 10, 960. |
| 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) | 21357 | (10R,11S,13S,17R)-17-[2-(acetoxy)acetyl]-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl acetate | C25H32O7 | 详情 | 详情 | |
| (III) | 21358 | 2-[(10R,11S,13S)-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15-decahydro-3H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl acetate | C23H28O5 | 详情 | 详情 | |
| (IV) | 21359 | (10R,11S,13S,16R,17S)-11-hydroxy-10,13-dimethyl-3-oxo-17-[3-(tetrahydro-2H-pyran-2-yloxy)propanoyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-16-carbonitrile | C28H37NO5 | 详情 | 详情 | |
| (V) | 21360 | methyl (10R,11S,13S,16R,17S)-17-glycoloyl-11-hydroxy-10,13-dimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-16-carboxylate | C23H30O6 | 详情 | 详情 |