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【结 构 式】 
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【分子编号】33652 【品名】(3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]octahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazole-2,6,8,14(1H,7H,9H)-tetrone 【CA登记号】 |
【 分 子 式 】C43H65N5O10 【 分 子 量 】812.0168 【元素组成】C 63.6% H 8.07% N 8.62% O 19.7% |
合成路线1
该中间体在本合成路线中的序号：(I)Direct fluorination of telithromycin (I) at position 2 by means of N-fluorosulfonimide and NaH afforded the title compound in low yield, along with a geater amount of the N-demethylated analogue. In a modified procedure, protection of the 2' hydroxyl group of (I) as the trimethylsilyl ether (II), followed by fluorination with N-fluorosulfonimide in the presence of potassium tert-butoxide provided fluoroketolide (III). Subsequent desilylation of (III) by means of tetrabutylammonium fluoride then furnished the title compound in high yield.
| 【1】 Bonnefoy, A.; Denis, A.; Novel fluoroketolides: Synthesis and antibacterial activity. Drugs Fut 2001, 26, 10, 975. |
| 【2】 Fromentin, C.; Denis, A.; Piltan, G.; Bretin, F.; Bonnet, A.; Agouridas, C.; Bonnefoy, A.; beta-Keto-ester chemistry and ketolides. Synthesis and antibacterial activity of 2-halogeno, 2-methyl and 2,3 enol-ether ketolides. Bioorg Med Chem Lett 2000, 10, 17, 2019. |
| 【3】 Spinnewyn, B.; Auguet, M.; Denis, A.; et al.; Synthesis and antibacterial activity of 2-halogeno, 2-methyl, and 2,3 enol-ether ketolides using beta-keto-ester chemistry. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2152. |
| 【4】 Agouridas, C.; Bretin, F.; Chantot, J.-F. (Aventis Pharma SA); Erythromycin derivs., their production and their use as medicaments. EP 0799833; JP 1997176182; US 5747467 . |
| 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) | 33652 | (3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]octahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazole-2,6,8,14(1H,7H,9H)-tetrone | C43H65N5O10 | 详情 | 详情 | |
| (II) | 33653 | (3aS,4R,7R,9R,10R,11R,13R,15R,15aR)-10-([(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]octahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazole-2,6,8,14(1H,7H,9H)-tetrone | C46H73N5O10Si | 详情 | 详情 | |
| (III) | 33654 | (3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-10-([(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-4-ethyl-7-fluoro-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]octahydro-2H-oxacyclotetradecino[4,3-d][1,3]oxazole-2,6,8,14(1H,7H,9H)-tetrone | C46H72FN5O10Si | 详情 | 详情 |