【结 构 式】 |
【分子编号】68891 【品名】(2R,3R,4S,6S)-6-(((3aR,4S,7S,8R,9R,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-10-(((2R,3S,4R,6S)-3-(benzoyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-8-yl)oxy)-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl benzoate 【CA登记号】 |
【 分 子 式 】C57H83N5O15 【 分 子 量 】1078.31 【元素组成】C 63.49% H 7.76% N 6.49% O 22.26% |
合成路线1
该中间体在本合成路线中的序号:(V)6-O-Methylerythromycin A (I) is protected with benzoic anhydride in the presence of triethylamine and DMAP in ethyl acetate to afford 2’,4”-di-O-benzoyl-6-O-methylerythromycin A (II). Treatment of the protected intermediate (II) with 1,8 diazabicyclo[5.4.0]undec-7-ene (DBU) followed by 1,1-carbonyldiimidazole (CDI) (III) in DMF yields 10,11-anhydro-2’,4”-di-O-benzoyl-12-O-imidazolylcarbonyl-6-Omethylerythromycin A (IV), which is converted to the 2’,4”-di-O-benzoyl-11-N-(4-azidobutyl)-6-O-methylerythromycin A 11,12-cyclic carbamate (V) by treatment with 4-azidobutylamine (XIII) and DBU in DMF. The cladinose sugar is cleaved from carbamate (V) by hydrolysis with 1 N HCl in acetone to provide 11-N-(4-azidobutyl)-5-(2’-benzoyldesosaminyl)-3-hydroxy-6-O-methylerythronolide A 11,12-cyclic carbamate (VI). 1-N-(4-Azidobutyl)-5-(2’-benzoyldesosaminyl)-3-oxo-6-O-methylerythronolide A 11,12-cyclic carbamate (VII) is prepared by oxidation of the secondary alcohol of intermediate (VI) with Dess-Martin periodinane (DMP).
【1】 Hwang, C., Duffield, J., Chiu, Y. et al. SAR of 11,12-carbamate macrolides/ketolides linked with 1,4-substituted-[1,2,3]-triazoles. 48th Intersci Conf Antimicrob Agents Chemother/Infect Dis Soc Am 46th Annu Meet (Oct 25-28, Washington, DC) 2008, Abst F1-3973. |
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) | 68888 | (3S,4R,5R,6S,7S,9S,11S,12S,13R,14S)-6- (((2R,3S,4R,6S)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-14-ethyl-12,13-dihydroxy-4-(((2S,4S,5R,6R)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-7-methoxy-3,5,7,9,11,13-hexamethyloxacyclotetradecane-2,10-dione | C38H69NO13 | 详情 | 详情 | |
(II) | 68889 | (2R,3R,4S,6S)-6-(((3S,4R,5R,6S,7S,9S,11S,12S,13R,14S)-6-(((2R,3S,4R,6S)-3-(benzoyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl)oxy)-14-ethyl-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecan-4-yl)oxy)-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl benzoate | C52H77NO15 | 详情 | 详情 | |
(III) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
(IV) | 68890 | (2S,3R,7S,9S,10S,11R,12R,13S)-10-(((2R,3S,4R,6S)-3-(benzoyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl)oxy)-12-(((2S,4S,5R,6R)-5-(benzoyloxy)-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl)oxy)-2-ethyl-9-methoxy-3,5,7,9,11,13-hexamethyl-6,14-dioxooxacyclotetradec-4-en-3-yl 1H-imidazole-1-carboxylate | C56H77N3O15 | 详情 | 详情 | |
(V) | 68891 | (2R,3R,4S,6S)-6-(((3aR,4S,7S,8R,9R,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-10-(((2R,3S,4R,6S)-3-(benzoyloxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-8-yl)oxy)-4-methoxy-2,4-dimethyltetrahydro-2H-pyran-3-yl benzoate | C57H83N5O15 | 详情 | 详情 | |
(VI) | 68892 | (2R,3S,4R,6S)-2-(((3aR,4S,7S,8R,9R,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-4-ethyl-8-hydroxy-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C42H65N5O11 | 详情 | 详情 | |
(VII) | 68893 | (2R,3S,4R,6S)-2-(((3aR,4S,7S,9S,10S,11S,13S,15S,15aS)-1-(4-azidobutyl)-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-2,6,8,14-tetraoxotetradecahydro-1H-[1]oxacyclotetradecino[4,3-d]oxazol-10-yl)oxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl benzoate | C42H63N5O11 | 详情 | 详情 | |
(XI) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
(XII) | 68896 | 1,4-diazidobutane | C4H8N6 | 详情 | 详情 | |
(XIII) | 68887 | azidobutylamine;4-azidobutan-1-amine | C4H10N4 | 详情 | 详情 |