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【结 构 式】 
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【分子编号】33511 【品名】(3R,8S,9S,10S,13S,14S,16R,17S)-17-acetyl-16-(acetoxy)-17-azido-10,13-dimethyl-11-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate; 17alpha-azido-3beta,16alpha-acetoxy-5alpha-pregnane-11,20-dione 【CA登记号】5167-90-8 |
【 分 子 式 】C25H35N3O6 【 分 子 量 】473.56952 【元素组成】C 63.41% H 7.45% N 8.87% O 20.27% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of 17alpha-azido-3beta,16alpha-acetoxy-5alpha-pregnane-11,20-dione (I) by hydrogenation with H2 over Pt in methanol, followed by a treatment with 10% HCl gives 3beta-hydroxy-5alpha-pregnane-11,20-dione-[17alpha,16alpha-d]-2'-methyloxazoline (II), which is converted into the semicarbazone (III) by treatment with semicarbazide hydrochloride (A) and pyridine in refluxing methanol. The reduction of one ketonic group of (III) with NaBH4 in refluxing ethanol yields the dihydroxy-semicarbazone (IV), which is hydrolyzed with 10% HCl in refluxing methanol to afford the ketodiol (V). The oxidation of (V) with cyclohexanone and aluminum isopropoxide in refluxing toluene gives 11beta-hydroxy-5alpha-pregnane-3,20-dione-[17alpha,16alpha-d]-2'-methyloxazoline (VI). The dehydrogenation of (VI) by treatment with Br2 in dioxane-acetic acid, followed by treatment with Li2CO3 in DMF at 140 C yields the corresponding 1,4-diene derivative (VII). Finally, the reaction of (VII) with I2 by means of azobisisobutyronitrile in CH2Cl2 affords the corresponding 21-iodo compound, which is then acetylated with triethylammonium acetate in refluxing acetone.
| 【1】 Nathansohn, G.; et al.; Steroids possessing nitrogen atoms. III. Synthesis of new highly active corticoids [17alpha,16alpha-d]-ozazolino steroids. J Med Chem 1967, 10, 5, 799. |
| 【2】 Castaner, J.; de Angelis, L.; Aclacinomycin A. Drugs Fut 1978, 3, 3, 171. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23944 | 1-Hydrazinecarboxamide | 563-41-7 | CH5N3O | 详情 | 详情 |
| (I) | 33511 | (3R,8S,9S,10S,13S,14S,16R,17S)-17-acetyl-16-(acetoxy)-17-azido-10,13-dimethyl-11-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate; 17alpha-azido-3beta,16alpha-acetoxy-5alpha-pregnane-11,20-dione | 5167-90-8 | C25H35N3O6 | 详情 | 详情 |
| (II) | 33512 | 3beta-hydroxy-5alpha-pregnane-11,20-dione-[17alpha,16alpha-d]-2'-methyloxazoline; (2R,4aS,4bS,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-2-hydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,4b,6,6a,6b,9a,10,10a,10b,11,12,12a-hexadecahydro-5H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-5-one | 5070-98-4 | C23H33NO4 | 详情 | 详情 |
| (III) | 33513 | 2-[(Z)-1-[(2R,4aS,4bS,6aS,9aR,10aS,10bS)-2-hydroxy-4a,6a,8-trimethyl-5-oxo-1,2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12,12a-hexadecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]ethylidene]-1-hydrazinecarboxamide | C24H36N4O4 | 详情 | 详情 | |
| (IV) | 33514 | 2-[(Z)-1-[(2R,4aS,4bS,5S,6aS,9aR,10aS,10bS)-2,5-dihydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12,12a-hexadecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]ethylidene]-1-hydrazinecarboxamide | C24H38N4O4 | 详情 | 详情 | |
| (V) | 33515 | 1-[(2R,4aS,4bS,5S,6aS,9aR,10aS,10bS)-2,5-dihydroxy-4a,6a,8-trimethyl-1,2,3,4,4a,4b,5,6,6a,9a,10,10a,10b,11,12,12a-hexadecahydro-6bH-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-6-yl]-1-ethanone | 13649-86-0 | C23H35NO4 | 详情 | 详情 |
| (VI) | 33516 | (4aS,4bS,5S,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-5-hydroxy-4a,6a,8-trimethyl-1,3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12,12a-hexadecahydro-2H-naphtho[2',1':4,5]indeno[1,2-d][1,3]oxazol-2-one; 11beta-hydroxy-5alpha-pregnane-3,20-dione-[17alpha,16alpha-d]-2’-methyloxazoline | C23H33NO4 | 详情 | 详情 | |
| (VII) | 33517 | (4aR,4bS,5S,6aS,6bS,9aR,10aS,10bS)-6b-acetyl-5-hydroxy-4a,6a,8-trimethyl-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]oxazol-2-one | 13649-88-2 | C23H29NO4 | 详情 | 详情 |
| (VIII) | 33518 | (4aR,4bS,5S,6aS,6bS,9aR,10aS,10bS)-5-hydroxy-6b-(2-iodoacetyl)-4a,6a,8-trimethyl-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]oxazol-2-one | C23H28INO4 | 详情 | 详情 |