【结 构 式】 |
【分子编号】45910 【品名】(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime] 【CA登记号】 |
【 分 子 式 】C45H82N2O14 【 分 子 量 】875.15116 【元素组成】C 61.76% H 9.44% N 3.2% O 25.59% |
合成路线1
该中间体在本合成路线中的序号:(IV)Treatment of erythromycin derivative (I) with hydroxylamine in isopropanol in the presence of HOAc affords oxime (II), which is then converted into the isopropoxycyclohexyl oxime form (IV) by reaction with 1,1-diisopropoxycyclohexane (III) and p-toluensulfonate (PPTS) in CH2Cl2. Regioselective protection of (IV) by means of N-(trimethylsilyl)-imidazole (Me3Si-Im) and chlorotrimethylsilane (TMSCl) in CH2Cl2 yields derivative (V), which is then converted into derivative (VI) by first methylation with methyl bromide and KOtBu in THF/methyl sulfoxide followed by deprotection with HOAc in acetonitrile. Oxime (VI) is then treated with sodium hydrosulfite (Na2S2O4) and formic acid in EtOH/H2O to provide derivative (VII).
【1】 Chu, D.; Grant, E.; Hlasta, D.; Henninger, T.; Khosla, C. (Kosan Biosciences, Inc.; Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0062783 . |
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) | 45907 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione | C36H65NO13 | 详情 | 详情 | |
(II) | 45908 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime | C36H66N2O13 | 详情 | 详情 | |
(III) | 45909 | 1-isopropoxycyclohexyl isopropyl ether; 1,1-diisopropoxycyclohexane | 1132-95-2 | C12H24O2 | 详情 | 详情 |
(IV) | 45910 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime] | C45H82N2O14 | 详情 | 详情 | |
(V) | 45911 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-([(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-7,12,13-trihydroxy-4-([(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime] | C51H98N2O14Si2 | 详情 | 详情 | |
(VI) | 45912 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime | C37H68N2O13 | 详情 | 详情 | |
(VII) | 45913 | (3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione | C37H67NO13 | 详情 | 详情 |