|
【结 构 式】 
|
【分子编号】14609 【品名】(5R,5aR,8aR,9S)-9-bromo-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one 【CA登记号】 |
【 分 子 式 】C21H19BrO7 【 分 子 量 】463.28166 【元素组成】C 54.44% H 4.13% Br 17.25% O 24.17% |
合成路线1
该中间体在本合成路线中的序号：(II)Podophyllotoxin (I), isolated from the roots of Podophyllum emodi Wall var. chinensis sprague by extraction with ethanol and purified through repeated recrystallization from ethanol-benzene, is demethylated and brominated in a single step. (I) is suspended in a cold mixture of ethylene dichloride and ether. Anhydrous hydrogen bromide is passed until the calculated weight increase is reached. After standing at 0-2 C for 20 hours, the solvent is removed under reduced pressure. 4-Bromo-4-deoxy-4'-demethylepipodophyllotoxin (II) is recrystallized from acetone. A solution of (II) and 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (III) with a trace of anhydrous pyridine in THF is refluxed under nitrogen atmosphere for 4 hours. The insoluble solid is removed by filtration and the solvent is distilled off under reduced pressure. The crude product is chromatographed twice through silica gel, using methylene chloride-acetone-diethylamine (40:1:1, by volume) as eluent. GP-7 is recrystallized from acetone-hexane.
| 【1】 Zhang, C.; Chen, Y.; Tian, X.; Spin-labeled antitumor derivatives of podophyllotoxin. Scientia Sin 1987, 30-B, 1070-9. |
| 【2】 Zhang, P.; Tian, X.; Li, J.; Wang, Y.; Chen, Y.; Jia, Z.; Anticancer drugs II. Synthesis and biological evaluation of spin labeled derivatives of podophyllotoxin. Life Sci 1989, 45, 26, 2569-75. |
| 【3】 Ruyun, J.; GP-7. Drugs Fut 1992, 17, 3, 191. |
| 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) | 14608 | (5R,5aR,8aR,9R)-9-hydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one; Podophyllotoxin | 518-28-5 | C22H22O8 | 详情 | 详情 |
| (II) | 14609 | (5R,5aR,8aR,9S)-9-bromo-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C21H19BrO7 | 详情 | 详情 | |
| (III) | 14610 | 4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol | 14691-88-4 | C9H19N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Oxidative oxidation of p-nitrobenzaldehyde (I) and 1,2-phenylenediamine (II) in DMF in the presence of nitrobenzene produced benzimidazole (III). Subsequent reduction of the nitro group of (III) by means of NaBH4 and CuCl afforded aniline (IV). Bromide (VI) was prepared by treatment of 4'-demethyl epipodophyllotoxin (V) with HBr. The title compound was then obtained by coupling aniline (IV) with bromide (VI) using BaCO3 in 1,2-dichloroethane.
| 【1】 Cheng, H.-H.; Guan, J.; Zhu, X.-K.; Cheng, Y.-C.; Tachibana, Y.; Bastow, K.F.; Lee, K.-H.; Gurwith, M.; Cho, S.J.; Antitumor agents. 194. Synthesis and biological evaluations of 4-beta-mono-, -di-, and -trisubstituted aniline-4'-O-demethyl-podophyllotoxin and related compounds with improved pharmacological profiles. J Med Chem 1999, 42, 13, 2441. |
| 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) | 18184 | 4-Nitrobenzaldehyde | 555-16-8 | C7H5NO3 | 详情 | 详情 |
| (II) | 12824 | 2-Aminophenylamine; o-Phenylenediamine; 1,2-Benzenediamine | 95-54-5 | C6H8N2 | 详情 | 详情 |
| (III) | 33735 | 2-(4-nitrophenyl)-1H-benzimidazole | C13H9N3O2 | 详情 | 详情 | |
| (IV) | 33736 | 4-(1H-benzimidazol-2-yl)aniline; 4-(1H-benzimidazol-2-yl)phenylamine | C13H11N3 | 详情 | 详情 | |
| (V) | 13053 | (5R,5aR,8aR,9S)-9-Hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | 6559-91-7 | C21H20O8 | 详情 | 详情 |
| (VI) | 14609 | (5R,5aR,8aR,9S)-9-bromo-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one | C21H19BrO7 | 详情 | 详情 |