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【结 构 式】 
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【分子编号】55088 【品名】(3R,4S,6R)-4-(dimethylamino)-2-{[(2R,3S,4R,5R,8R,10R,11R,12R,14R)-2-ethyl-3,4-dihydroxy-10-methoxy-3,5,8,10,12,14-hexamethyl-6,13,15-trioxo-1-oxa-7-azacyclopentadecan-11-yl]oxy}-6-methyltetrahydro-2H-pyran-3-yl acetate 【CA登记号】 |
【 分 子 式 】C32H56N2O11 【 分 子 量 】644.80352 【元素组成】C 59.61% H 8.75% N 4.34% O 27.29% |
合成路线1
该中间体在本合成路线中的序号：(VI)6-O-Methylerythromycin A (I) was converted to a mixture of (E)- and (Z)-oximes upon treatment with hydroxylamine in refluxing MeOH. Beckmann rearrangement of the required (Z)-isomer (II) in the presence of tosyl chloride and NaHCO3 led to the macrocyclic lactam (III). Smooth acidic hydrolysis of (III) selectively removed the 3-cladinose moiety, yielding (IV). The 3-decladinosyl derivative (IV) was then protected as the 2' acetate (V) employing Ac2O in the presence of NaHCO3. Subsequent oxidation of the 3-hydroxyl group of (V) under modified Swern conditions furnished ketone (VI). Finally, methanolysis of the acetate ester group of (VI) provided the title compound.
| 【1】 Alihodzic, S.; et al.; Synthesis and antibacterial activity of isomeric 15-membered azalides. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2001, Abst 1177. |
| 【2】 Kobrehel, G.; Lazarevski, G.; Kelneric, Z. (Pliva dd); 15-Membered lactams ketolides with antibacterial activity. EP 1070077; JP 2002510701; US 6110965; WO 9951616 . |
| 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) | 18631 | (3R,4S,5R,6R,7R,9R,11R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-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-hexamethyl-2,10-oxacyclotetradecanedione | C38H69NO13 | 详情 | 详情 | |
| (II) | 55084 | (3R,4S,5R,6R,7R,9R,11S,12R,13S,14R)-6-{[(3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-14-ethyl-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-hexamethyl-2,10-oxacyclotetradecanedione 10-oxime | C38H70N2O13 | 详情 | 详情 | |
| (III) | 55085 | (2R,3S,4R,5R,8R,10R,11R,12R,13S,14R)-11-{[(3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-2-ethyl-3,4-dihydroxy-13-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy}-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-7-azacyclopentadecane-6,15-dione | C38H70N2O13 | 详情 | 详情 | |
| (IV) | 55086 | (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-11-{[(3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy}-2-ethyl-3,4,13-trihydroxy-10-methoxy-3,5,8,10,12,14-hexamethyl-1-oxa-7-azacyclopentadecane-6,15-dione | C30H56N2O10 | 详情 | 详情 | |
| (V) | 55087 | (3R,4S,6R)-4-(dimethylamino)-2-{[(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-2-ethyl-3,4,13-trihydroxy-10-methoxy-3,5,8,10,12,14-hexamethyl-6,15-dioxo-1-oxa-7-azacyclopentadecan-11-yl]oxy}-6-methyltetrahydro-2H-pyran-3-yl acetate | C32H58N2O11 | 详情 | 详情 | |
| (VI) | 55088 | (3R,4S,6R)-4-(dimethylamino)-2-{[(2R,3S,4R,5R,8R,10R,11R,12R,14R)-2-ethyl-3,4-dihydroxy-10-methoxy-3,5,8,10,12,14-hexamethyl-6,13,15-trioxo-1-oxa-7-azacyclopentadecan-11-yl]oxy}-6-methyltetrahydro-2H-pyran-3-yl acetate | C32H56N2O11 | 详情 | 详情 |