泰利霉素和喹红霉素工艺.doc

中文名称 泰利霉素 别名 红霉酮(特利霉素) 英文名称 ?Telithromycin 英文别名 ? KETEK; (1R,2R,4R,6S,7R,8R,10R,13R,14S)-7-[(2S,3R,4S,6R)-4-Dimethylamino-3-hydroxy-6-methyloxan-2-yl]oxy-13-ethyl-6-methoxy- 2,4,6,8,10,14-hexamethyl-17-[4-(4-pyridin-3-ylimidazol-1-yl)butyl]-12,15-dioxa- 17-azabicyclo[12.3.0]heptadecane-3,9,11,16-tetrone CAS NO. ?191114-48-4 EINECS ? 分子式 C43H65N5O10 分子结构图 【药物名称】Telithromycin, RU-66647, HMR-3647, Levviax, Ketek 化学结构式(Chemical Structure): 参考文献No. 28301 标题: Novel erythromycin derivs., method for their preparation and their use as drugs 作者: Agouridas, C.; Chantot, J.-F.; Denis, A.; Gouin dAmbrieres, S.; Le Martret, O. (Aventis Pharma SA) 来源: EP 0680967; FR 2719587; JP 1996053489; JP 1999152296; US 5635485; WO 9529929 合成路线图解说明: The selective mesylation of 2-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyloxy)-6-O-methyl-3-oxoerythromycin A (I) with methanesulfonic anhydride in pyridine gives the expected 11-O-methanesulfonyl derivative (II), which is treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone to yield the 10,11-didehydro derivative (III). The acylation of (III) with carbonyl diimidazole (IV) by means of NaH in THF affords the 12-O-acyl derivative (V), which is finally cyclocondensed with 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) in hot acetonitrile. The intermediate compound 4-[4-(3-pyridyl)imidazol-1-yl]butylamine (VI) is obtained as follows: The condensation of N-(4-bromobutyl)phthalimide (VII) with 4-(3-pyridyl)imidazole (VIII) by means of NaH in DMF gives N-[4-[4-(3-pyridyl)imidazol-1-yl]butyl]phthalimide (IX), which is then treated with hydrazine in refluxing ethanol. 参考文献No. 34565 标题: Novel erythromycin derivs., their process of preparation and their application as medicines 作者: Agouridas, C.; Chantot, J.F.; Denis, A.; Gouin dAmbrieres, S.; Le Martret, O. (Aventis Pharma SA) 来源: FR 2732684 合成路线图解说明: The selective mesylation of 2-O-acetyl-3-des(2,6-dideoxy-3-C-methyl-3-O-methyl-alph